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Photoresponsive biomaterials for targeted drug delivery and 4D cell culture

Nature Reviews Materials volume 3, Article number: 17087 (2018) Cite this article

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Abstract

Biological signalling is regulated through a complex and tightly choreographed interplay between cells and their extracellular matrix. The spatiotemporal control of these interactions is essential for tissue function, and disruptions to this dialogue often result in aberrant cell fate and disease. When disturbances are well understood, correct biological function can be restored through the precise introduction of therapeutics. Moreover, model systems with modifiable physiochemical properties are needed to probe the effects of therapeutic molecules and to investigate cell–matrix interactions. Photoresponsive biomaterials benefit from spatiotemporal tunability, which allows for site-specific therapeutic delivery in vivo and 4D modulation of synthetic cell culture platforms to mimic the dynamic heterogeneity of the human body in vitro. In this Review, we discuss how light can be exploited to modify different biomaterials in the context of photomediated drug delivery and phototunable cell culture platforms. We survey various photochemistries for their applicability in vitro and in vivo and for the biochemical and biophysical modification of materials. Finally, we highlight emerging tools and provide an outlook for the field of photoresponsive biomaterials.

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Figure 1: Photoresponsive biomaterials as platforms for targeted drug delivery and 4D cell culture.
Figure 2: Photocontrolled delivery of bioactive molecules.
Figure 3: Photomediated biochemical alteration of biomaterials.
Figure 4: Photomediated biophysical alteration of biomaterials.
Figure 5: Independent physiochemical tuning of biomaterials to mimic in vivo processes.

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References

  1. Palczewski, K. Chemistry and biology of vision. J. Biol. Chem. 287, 1612–1619 (2012).

    Article  CAS  Google Scholar 

  2. Brieke, C., Rohrbach, F., Gottschalk, A., Mayer, G. & Heckel, A. Light-controlled tools. Angew. Chem. Int. Ed. 51, 8446–8476 (2012).

    Article  CAS  Google Scholar 

  3. Yu, H., Li, J., Wu, D., Qiu, Z. & Zhang, Y. Chemistry and biological applications of photo-labile organic molecules. Chem. Soc. Rev. 39, 464–473 (2010).

    Article  Google Scholar 

  4. Zhu, C., Ninh, C. & Bettinger, C. J. Photoreconfigurable polymers for biomedical applications: chemistry and macromolecular engineering. Biomacromolecules 15, 3474–3494 (2014).

    Article  CAS  Google Scholar 

  5. Cui, J., Miguel, V. S. & del Campo, A. Light-triggered multifunctionality at surfaces mediated by photolabile protecting groups. Macromol. Rapid Commun. 34, 310–329 (2013).

    Article  CAS  Google Scholar 

  6. Kaplan, J. H., Forbush, B. & Hoffman, J. F. Rapid photolytic release of adenosine 5′-triphosphate from a protected analog: utilization by the sodium:potassium pump of human red blood cell ghosts. Biochemistry 17, 1929–1935 (1978).

    Article  CAS  Google Scholar 

  7. Klán, P. et al. Photoremovable protecting groups in chemistry and biology: reaction mechanisms and efficacy. Chem. Rev. 113, 119–191 (2013).

    Article  CAS  Google Scholar 

  8. Ercole, F., Davis, T. P. & Evans, R. A. Photo-responsive systems and biomaterials: photochromic polymers, light-triggered self-assembly, surface modification, fluorescence modulation and beyond. Polym. Chem. 1, 37–54 (2010).

    Article  CAS  Google Scholar 

  9. Wang, Y., Shim, M. S., Levinson, N. S., Sung, H.-W. & Xia, Y. Stimuli-responsive materials for controlled release of theranostic agents. Adv. Funct. Mater. 24, 4206–4220 (2014).

    Article  CAS  Google Scholar 

  10. Barhoumi, A., Liu, Q. & Kohane, D. S. Ultraviolet light-mediated drug delivery: principles, applications, and challenges. J. Control. Release 219, 31–42 (2015).

    Article  CAS  Google Scholar 

  11. Velema, W. A., Szymanski, W. & Feringa, B. L. Photopharmacology: beyond proof of principle. J. Am. Chem. Soc. 136, 2178–2191 (2014).

    Article  CAS  Google Scholar 

  12. Olejniczak, J., Carling, C.-J. & Almutairi, A. Photocontrolled release using one-photon absorption of visible or NIR light. J. Control. Release 219, 18–30 (2015).

    Article  CAS  Google Scholar 

  13. Breitinger, H.-G. A., Wieboldt, R., Ramesh, D., Carpenter, B. K. & Hess, G. P. Synthesis and characterization of photolabile derivatives of serotonin for chemical kinetic investigations of the serotonin 5-HT 3 receptor. Biochemistry 39, 5500–5508 (2000).

    Article  CAS  Google Scholar 

  14. Shi, Y. et al. Light-triggered release of ciprofloxacin from an in situ forming click hydrogel for antibacterial wound dressings. J. Mater. Chem. B 3, 8771–8774 (2015).

    Article  CAS  Google Scholar 

  15. Paul, A. et al. Photoresponsive real time monitoring silicon quantum dots for regulated delivery of anticancer drugs. J. Mater. Chem. B 4, 521–528 (2016).

    Article  CAS  Google Scholar 

  16. Cabane, E., Malinova, V., Menon, S., Palivan, C. G. & Meier, W. Photoresponsive polymersomes as smart, triggerable nanocarriers. Soft Matter 7, 9167–9176 (2011).

    Article  CAS  Google Scholar 

  17. Kohman, R. E., Cha, S. S., Man, H.-Y. & Han, X. Light-triggered release of bioactive molecules from DNA nanostructures. Nano Lett. 16, 2781–2785 (2016).

    Article  CAS  Google Scholar 

  18. Shestopalov, I. A., Sinha, S. & Chen, J. K. Light-controlled gene silencing in zebrafish embryos. Nat. Chem. Biol. 3, 650–651 (2007).

    Article  CAS  Google Scholar 

  19. Inlay, M. A. et al. Synthesis of a photocaged tamoxifen for light-dependent activation of Cre-ER recombinase-driven gene modification. Chem. Commun. 49, 4971–4973 (2013).

    Article  CAS  Google Scholar 

  20. Li, L. et al. Aptamer photoregulation in vivo. Proc. Natl Acad. Sci. USA 111, 17099–17103 (2014).

    Article  CAS  Google Scholar 

  21. Huynh, C. T. et al. Photocleavable hydrogels for light-triggered siRNA release. Adv. Healthc. Mater. 5, 305–310 (2015).

    Article  CAS  Google Scholar 

  22. Faal, T. et al. 4-Hydroxytamoxifen probes for light-dependent spatiotemporal control of Cre-ER mediated reporter gene expression. Mol. Biosyst. 11, 783–790 (2015).

    Article  CAS  Google Scholar 

  23. Sarode, B. R., Kover, K., Tong, P. Y., Zhang, C. & Friedman, S. H. Light control of insulin release and blood glucose using an injectable photoactivated depot. Mol. Pharm. 13, 3835–3841 (2016).

    Article  CAS  Google Scholar 

  24. D'souza, A. J. M. & Topp, E. M. Release from polymeric prodrugs: linkages and their degradation. J. Pharm. Sci. 93, 1962–1979 (2004).

    Article  CAS  Google Scholar 

  25. Fomina, N., McFearin, C., Sermsakdi, M., Edigin, O. & Almutairi, A. UV and near-IR triggered release from polymeric nanoparticles. J. Am. Chem. Soc. 132, 9540–9542 (2010).

    Article  CAS  Google Scholar 

  26. Huu, V. A. N. et al. Light-responsive nanoparticle depot to control release of a small molecule angiogenesis inhibitor in the posterior segment of the eye. J. Control. Release 200, 71–77 (2015). This study reports the first in vivo therapeutic release from photodegradable polymeric nanoparticles in the eye.

    Article  CAS  Google Scholar 

  27. Aujard, I. et al. o-Nitrobenzyl photolabile protecting groups with red-shifted absorption: syntheses and uncaging cross-sections for one- and two-photon excitation. Chem. Eur. J. 12, 6865–6879 (2006).

    Article  CAS  Google Scholar 

  28. Holmes, C. P. Model studies for new o-nitrobenzyl photolabile linkers: substituent effects on the rates of photochemical cleavage. J. Org. Chem. 62, 2370–2380 (1997).

    Article  CAS  Google Scholar 

  29. Griffin, D. R. & Kasko, A. M. Photoselective delivery of model therapeutics from hydrogels. ACS Macro Lett. 1, 1330–1334 (2012). This study describes the wavelength-selective release of multiple therapeutics from a single biomaterial.

    Article  CAS  Google Scholar 

  30. Donato, L. et al. Water-soluble, donor-acceptor biphenyl derivatives in the 2-(o-nitrophenyl)propyl series: highly efficient two-photon uncaging of the neurotransmitter γ-aminobutyric acid at λ + 800 nm. Angew. Chem. Int. Ed. 51, 1840–1843 (2012).

    Article  CAS  Google Scholar 

  31. Olejniczak, J., Sankaranarayanan, J., Viger, M. L. & Almutairi, A. Highest efficiency two-photon degradable copolymer for remote controlled release. ACS Macro Lett. 2, 683–687 (2013).

    Article  CAS  Google Scholar 

  32. Carling, C.-J. et al. Efficient red light photo-uncaging of active molecules in water upon assembly into nanoparticles. Chem. Sci. 7, 2392–2398 (2015).

    Article  CAS  Google Scholar 

  33. Yang, Y. et al. NIR light controlled photorelease of siRNA and its targeted intracellular delivery based on upconversion nanoparticles. Nanoscale 5, 231–238 (2013).

    Article  CAS  Google Scholar 

  34. Yang, Y., Velmurugan, B., Liu, X. & Xing, B. NIR photoresponsive crosslinked upconverting nanocarriers toward selective intracellular drug release. Small 9, 2937–2944 (2013).

    Article  CAS  Google Scholar 

  35. Wang, W. et al. Efficient triplet-triplet annihilation-based upconversion for nanoparticle phototargeting. Nano Lett. 15, 6332–6338 (2015).

    Article  CAS  Google Scholar 

  36. Yan, B., Boyer, J.-C., Branda, N. R. & Zhao, Y. Near-infrared light-triggered dissociation of block copolymer micelles using upconverting nanoparticles. J. Am. Chem. Soc. 133, 19714–19717 (2011).

    Article  CAS  Google Scholar 

  37. Yan, B., Boyer, J.-C., Habault, D., Branda, N. R. & Zhao, Y. Near infrared light triggered release of biomacromolecules from hydrogels loaded with upconversion nanoparticles. J. Am. Chem. Soc. 134, 16558–16561 (2012).

    Article  CAS  Google Scholar 

  38. Sudimack, J. & Lee, R. J. Targeted drug delivery via the folate receptor. Adv. Drug Deliv. Rev. 41, 147–162 (2000).

    Article  CAS  Google Scholar 

  39. Fan, N.-C., Cheng, F.-Y., Ho, J. A. & Yeh, C.-S. Photocontrolled targeted drug delivery: photocaged biologically active folic acid as a light-responsive tumor-targeting molecule. Angew. Chem. Int. Ed. 51, 8806–8810 (2012).

    Article  CAS  Google Scholar 

  40. Choi, S. K. et al. Light-controlled release of caged doxorubicin from folate receptor-targeting PAMAM dendrimer nanoconjugate. Chem. Commun. 46, 2632–2634 (2010).

    Article  CAS  Google Scholar 

  41. Hu, X., Tian, J., Liu, T., Zhang, G. & Liu, S. Photo-triggered release of caged camptothecin prodrugs from dually responsive shell cross-linked micelles. Macromolecules 46, 6243–6256 (2013).

    Article  CAS  Google Scholar 

  42. Azagarsamy, M. A., Alge, D. L., Radhakrishnan, S. J., Tibbitt, M. W. & Anseth, K. S. Photocontrolled nanoparticles for on-demand release of proteins. Biomacromolecules 13, 2219–2224 (2012).

    Article  CAS  Google Scholar 

  43. Koren, E. & Torchilin, V. P. Cell-penetrating peptides: breaking through to the other side. Trends Mol. Med. 18, 385–393 (2012).

    Article  CAS  Google Scholar 

  44. Shamay, Y., Adar, L., Ashkenasy, G. & David, A. Light induced drug delivery into cancer cells. Biomaterials 32, 1377–1386 (2011).

    Article  CAS  Google Scholar 

  45. Yang, Y. Y., Yang, Y. Y., Xie, X., Cai, X. & Mei, X. Preparation and characterization of photo-responsive cell-penetrating peptide-mediated nanostructured lipid carrier. J. Drug Target. 22, 891–900 (2014).

    Article  CAS  Google Scholar 

  46. Lin, W. et al. Enhanced small interfering RNA delivery into cells by exploiting the additive effect between photo-sensitive peptides and targeting ligands. J. Pharm. Pharmacol. 67, 1215–1231 (2015).

    Article  CAS  Google Scholar 

  47. Badeau, B. A., Comerford, M. P., Arakawa, C. K., Shadish, J. A. & DeForest, C. A. Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery. Nat. Chem.http://dx.doi.org/10.1038/nchem.2917 (2018).

  48. Lee, J. S., Deng, X., Han, P. & Cheng, J. Dual stimuli-responsive poly(β-amino ester) nanoparticles for on-demand burst release. Macromol. Biosci. 15, 1314–1322 (2015).

    Article  CAS  Google Scholar 

  49. Liu, G., Zhou, L., Guan, Y., Su, Y. & Dong, C.-M. Multi-responsive polypeptidosome: characterization, morphology transformation, and triggered drug delivery. Macromol. Rapid Commun. 35, 1673–1678 (2014).

    Article  CAS  Google Scholar 

  50. Klinger, D. & Landfester, K. Dual stimuli-responsive poly(2-hydroxyethyl methacrylate-co-methacrylic acid) microgels based on photo-cleavable cross-linkers: pH-dependent swelling and light-induced degradation. Macromolecules 44, 9758–9772 (2011). This study describes multi-stimuli-responsive drug delivery for differential release profiles of a single therapeutic.

    Article  CAS  Google Scholar 

  51. Zhang, Y. et al. Polymer-coated hollow mesoporous silica nanoparticles for triple-responsive drug delivery. ACS Appl. Mater. Interfaces 7, 18179–18187 (2015).

    Article  CAS  Google Scholar 

  52. Givens, R. S. & Matuszewski, B. Photochemistry of phosphate esters: an efficient method for the generation of electrophiles. J. Am. Chem. Soc. 106, 6860–6861 (1984).

    Article  CAS  Google Scholar 

  53. Suzuki, A. Z. et al. Coumarin-4-ylmethoxycarbonyls as phototriggers for alcohols and phenols. Org. Lett. 5, 4867–4870 (2003).

    Article  CAS  Google Scholar 

  54. Geissler, D. et al. (Coumarin-4-yl)methyl esters as highly efficient, ultrafast phototriggers for protons and their application to acidifying membrane surfaces. Angew. Chem. Int. Ed. 44, 1195–1198 (2005).

    Article  CAS  Google Scholar 

  55. Jin, Q., Mitschang, F. & Agarwal, S. Biocompatible drug delivery system for photo-triggered controlled release of 5-fluorouracil. Biomacromolecules 12, 3684–3691 (2011).

    Article  CAS  Google Scholar 

  56. Huang, Q., Bao, C., Ji, W., Wang, Q. & Zhu, L. Photocleavable coumarin crosslinkers based polystyrene microgels: phototriggered swelling and release. J. Mater. Chem. 22, 18275 (2012).

    Article  CAS  Google Scholar 

  57. Mal, N. K., Fujiwara, M., Tanaka, Y., Taguchi, T. & Matsukata, M. Photo-switched storage and release of guest molecules in the pore void of coumarin-modified MCM-41. Chem. Mater. 15, 3385–3394 (2003).

    Article  CAS  Google Scholar 

  58. Lin, Q. et al. Anticancer drug release from a mesoporous silica based nanophotocage regulated by either a one- or two-photon process. J. Am. Chem. Soc. 132, 10645–10647 (2010).

    Article  CAS  Google Scholar 

  59. Ji, W. et al. Coumarin-containing photo-responsive nanocomposites for NIR light-triggered controlled drug release via a two-photon process. J. Mater. Chem. B 1, 5942 (2013).

    Article  CAS  Google Scholar 

  60. Ando, H., Furuta, T., Tsien, R. Y. & Okamoto, H. Photo-mediated gene activation using caged RNA/DNA in zebrafish embryos. Nat. Genet. 28, 317–325 (2001).

    Article  CAS  Google Scholar 

  61. Seo, H. J. & Kim, J.-C. 7-Acetoxycoumarin dimer-incorporated and folate-decorated liposomes: photoresponsive release and in vitro targeting and efficacy. Bioconjug. Chem. 25, 533–542 (2014).

    Article  CAS  Google Scholar 

  62. Long, Y.-B., Gu, W.-X., Pang, C., Ma, J. & Gao, H. Construction of coumarin-based cross-linked micelles with pH responsive hydrazone bond and tumor targeting moiety. J. Mater. Chem. B 4, 1480–1488 (2016).

    Article  CAS  Google Scholar 

  63. Ohtsuki, T. et al. Phototriggered protein syntheses by using (7-diethylaminocoumarin-4-yl)methoxycarbonyl-caged aminoacyl tRNAs. Nat. Commun. 7, 12501 (2016).

    Article  CAS  Google Scholar 

  64. Lin, Q. et al. Highly discriminating photorelease of anticancer drugs based on hypoxia activatable phototrigger conjugated chitosan nanoparticles. Adv. Mater. 25, 1981–1986 (2013).

    Article  CAS  Google Scholar 

  65. Fournier, L. et al. A blue-absorbing photolabile protecting group for in vivo chromatically orthogonal photoactivation. ACS Chem. Biol. 8, 1528–1536 (2013).

    Article  CAS  Google Scholar 

  66. Fournier, L. et al. Coumarinylmethyl caging groups with redshifted absorption. Chem. Eur. J. 19, 17494–17507 (2013).

    Article  CAS  Google Scholar 

  67. Furuta, T. et al. Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis. Proc. Natl Acad. Sci. USA 96, 1193–1200 (1999).

    Article  CAS  Google Scholar 

  68. Babin, J. et al. A new two-photon-sensitive block copolymer nanocarrier. Angew. Chem. Int. Ed. 48, 3329–3332 (2009).

    Article  CAS  Google Scholar 

  69. Kumar, S. et al. Near-infrared light sensitive polypeptide block copolymer micelles for drug delivery. J. Mater. Chem. 22, 7252 (2012).

    Article  CAS  Google Scholar 

  70. Lux, C. d. G et al. Short soluble coumarin crosslinkers for light-controlled release of cells and proteins from hydrogels. Biomacromolecules 16, 3286–3296 (2015).

    Article  CAS  Google Scholar 

  71. Bandara, H. M. D. & Burdette, S. C. Photoisomerization in different classes of azobenzene. Chem. Soc. Rev. 41, 1809–1825 (2012).

    Article  CAS  Google Scholar 

  72. Kano, K. et al. Photoresponsive membranes. Regulation of membrane properties by photoreversible cis-trans isomerization of azobenzenes. Chem. Lett. 9, 421–424 (1980).

    Article  Google Scholar 

  73. Bisby, R. H., Mead, C. & Morgan, C. G. Active uptake of drugs into photosensitive liposomes and rapid release on UV photolysis. Photochem. Photobiol. 72, 57–61 (2000).

    Article  CAS  Google Scholar 

  74. Wang, Y. et al. Photocontrolled self-assembly and disassembly of block ionomer complex vesicles: a facile approach toward supramolecular polymer nanocontainers. Langmuir 26, 709–715 (2010).

    Article  CAS  Google Scholar 

  75. Zhang, H. et al. Reversible morphology transitions of supramolecular polymer self-assemblies for switch-controlled drug release. Chem. Commun. 51, 15366–15369 (2015).

    Article  CAS  Google Scholar 

  76. Liu, D., Wang, S., Xu, S. & Liu, H. Photocontrollable intermittent release of doxorubicin hydrochloride from liposomes embedded by azobenzene-contained glycolipid. Langmuir 33, 1004–1012 (2017).

    Article  CAS  Google Scholar 

  77. Sheldon, J. E., Dcona, M. M., Lyons, C. E., Hackett, J. C. & Hartman, M. C. T. Photoswitchable anticancer activity via trans-cis isomerization of a combretastatin A-4 analog. Org. Biomol. Chem. 14, 40–49 (2015).

    Article  Google Scholar 

  78. Angelos, S., Choi, E., Vogtle, F., DeCola, L. & Zink, J. I. Photo-driven expulsion of molecules from mesostructured silica nanoparticles. J. Phys. Chem. C 111, 6589–6592 (2007).

    Article  CAS  Google Scholar 

  79. Lu, J., Choi, E., Tamanoi, F. & Zink, J. I. Light-activated nanoimpeller-controlled drug release in cancer cells. Small 4, 421–426 (2008).

    Article  CAS  Google Scholar 

  80. Guardado-Alvarez, T. M., Sudha Devi, L., Russell, M. M., Schwartz, B. J. & Zink, J. I. Activation of snap-top capped mesoporous silica nanocontainers using two near-infrared photons. J. Am. Chem. Soc. 135, 14000–14003 (2013).

    Article  CAS  Google Scholar 

  81. Tarn, D. et al. A reversible light-operated nanovalve on mesoporous silica nanoparticles. Nanoscale 6, 3335–3343 (2014).

    Article  CAS  Google Scholar 

  82. Zhu, Y. & Fujiwara, M. Installing dynamic molecular photomechanics in mesopores: a multifunctional controlled-release nanosystem. Angew. Chem. Int. Ed. 46, 2241–2244 (2007).

    Article  CAS  Google Scholar 

  83. Yuan, Q. et al. Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid. ACS Nano 6, 6337–6344 (2012).

    Article  CAS  Google Scholar 

  84. Liu, J., Bu, W., Pan, L. & Shi, J. NIR-triggered anticancer drug delivery by upconverting nanoparticles with integrated azobenzene-modified mesoporous silica. Angew. Chem. Int. Ed. 52, 4375–4379 (2013).

    Article  CAS  Google Scholar 

  85. Bléger, D., Schwarz, J., Brouwer, A. M. & Hecht, S. o-Fluoroazobenzenes as readily synthesized photoswitches offering nearly quantitative two-way isomerization with visible light. J. Am. Chem. Soc. 134, 20597–20600 (2012).

    Article  CAS  Google Scholar 

  86. Knie, C. et al. ortho-fluoroazobenzenes: visible light switches with very long-lived Z isomers. Chem. Eur. J. 20, 16492–16501 (2014).

    Article  CAS  Google Scholar 

  87. Konrad, D. B., Frank, J. A. & Trauner, D. Synthesis of redshifted azobenzene photoswitches by late-stage functionalization. Chem. Eur. J. 22, 4364–4368 (2016).

    Article  CAS  Google Scholar 

  88. Frank, J. A. et al. Photoswitchable fatty acids enable optical control of TRPV1. Nat. Commun. 6, 7118 (2015).

    Article  Google Scholar 

  89. Broichhagen, J., Frank, J. A. & Trauner, D. A. Roadmap to success in photopharmacology. Acc. Chem. Res. 48, 1947–1960 (2015).

    Article  CAS  Google Scholar 

  90. Dong, M., Babalhavaeji, A., Samanta, S., Beharry, A. A. & Woolley, G. A. Red-shifting azobenzene photoswitches for in vivo use. Acc. Chem. Res. 48, 2662–2670 (2015).

    Article  CAS  Google Scholar 

  91. Achilleos, D. S., Hatton, T. A. & Vamvakaki, M. Light-regulated supramolecular engineering of polymeric nanocapsules. J. Am. Chem. Soc. 134, 5726–5729 (2012).

    Article  CAS  Google Scholar 

  92. Son, S., Shin, E. & Kim, B.-S. Light-responsive micelles of spiropyran initiated hyperbranched polyglycerol for smart drug delivery. Biomacromolecules 15, 628–634 (2014).

    Article  CAS  Google Scholar 

  93. Chen, S., Jiang, F., Cao, Z., Wang, G. & Dang, Z.-M. Photo, pH, and thermo triple-responsive spiropyran-based copolymer nanoparticles for controlled release. Chem. Commun. 51, 12633–12636 (2015).

    Article  CAS  Google Scholar 

  94. Chen, S. et al. Nanocomposites of spiropyran-functionalized polymers and upconversion nanoparticles for controlled release stimulated by near-infrared light and pH. Macromolecules 49, 7490–7496 (2016).

    Article  CAS  Google Scholar 

  95. Chang, D., Yan, W., Yang, Y., Wang, Q. & Zou, L. Reversible light-controllable intelligent gel based on simple spiropyran-doped with biocompatible lecithin. Dye. Pigment. 134, 186–189 (2016).

    Article  CAS  Google Scholar 

  96. Tong, R., Hemmati, H. D., Langer, R. & Kohane, D. S. Photoswitchable nanoparticles for triggered tissue penetration and drug delivery. J. Am. Chem. Soc. 134, 8848–8855 (2012). This study describes photoisomerization-directed release for repetitive dosing deep within tissue.

    Article  CAS  Google Scholar 

  97. Tong, R., Chiang, H. H. & Kohane, D. S. Photoswitchable nanoparticles for in vivo cancer chemotherapy. Proc. Natl Acad. Sci. USA 110, 19048–19053 (2013).

    Article  CAS  Google Scholar 

  98. Wolff, L. About diazoanhydrides. Liebigs Ann. Chemie 325, 129–195 (1902).

    Article  Google Scholar 

  99. Urdabayev, N. K. & Popik, V. V. Wolff rearrangement of 2-diazo-1(2H)-naphthalenone induced by nonresonant two-photon absorption of NIR radiation. J. Am. Chem. Soc. 126, 4058–4059 (2004).

    Article  CAS  Google Scholar 

  100. Goodwin, A. P., Mynar, J. L., Ma, Y., Fleming, G. R. & Fréchet, J. M. J. Synthetic micelle sensitive to IR light via a two-photon process. J. Am. Chem. Soc. 127, 9952–9953 (2005).

    Article  CAS  Google Scholar 

  101. Mynar, J. L. et al. Two-photon degradable supramolecular assemblies of linear-dendritic copolymers. Chem. Commun. 2081–2082 (2007).

  102. Sun, L., Yang, Y., Dong, C.-M. & Wei, Y. Two-photon-sensitive and sugar-targeted nanocarriers from degradable and dendritic amphiphiles. Small 7, 401–406 (2011).

    Article  CAS  Google Scholar 

  103. Yuan, Y. et al. Conjugated polymer and drug co-encapsulated nanoparticles for chemo- and photo-thermal combination therapy with two-photon regulated fast drug release. Nanoscale 7, 3067–3076 (2015).

    Article  CAS  Google Scholar 

  104. Ahmad, R., Fu, J., He, N. & Li, S. Advanced gold nanomaterials for photothermal therapy of cancer. J. Nanosci. Nanotechnol. 15, 1–14 (2015).

    Article  CAS  Google Scholar 

  105. Gu, L., Koymen, A. R. & Mohanty, S. K. Crystalline magnetic carbon nanoparticle assisted photothermal delivery into cells using CW near-infrared laser beam. Sci. Rep. 4, 5106 (2014).

    Article  CAS  Google Scholar 

  106. Febvay, S., Marini, D. M., Belcher, A. M. & Clapham, D. E. Targeted cytosolic delivery of cell-impermeable compounds by nanoparticle-mediated, light-triggered endosome disruption. Nano Lett. 10, 2211–2219 (2010).

    Article  CAS  Google Scholar 

  107. Vivero-Escoto, J. L., Slowing, I. I., Wu, C.-W. & Lin, V. S.-Y. Photoinduced intracellular controlled release drug delivery in human cells by gold-capped mesoporous silica nanosphere. J. Am. Chem. Soc. 131, 3462–3463 (2009).

    Article  CAS  Google Scholar 

  108. Troutman, T. S., Leung, S. J. & Romanowski, M. Light-induced content release from plasmon resonant liposomes. Adv. Mater. 21, 2334–2338 (2009).

    Article  CAS  Google Scholar 

  109. Yavuz, M. S. et al. Gold nanocages covered by smart polymers for controlled release with near-infrared light. Nat. Mater. 8, 935–939 (2009).

    Article  CAS  Google Scholar 

  110. Rengan, A. K., Jagtap, M., De, A., Banerjee, R. & Srivastava, R. Multifunctional gold coated thermo-sensitive liposomes for multimodal imaging and photo-thermal therapy of breast cancer cells. Nanoscale 6, 916–923 (2014).

    Article  CAS  Google Scholar 

  111. Basuki, J. S. et al. Photo-modulated therapeutic protein release from a hydrogel depot using visible light. Angew. Chem. Int. Ed. 56, 966–971 (2017).

    Article  CAS  Google Scholar 

  112. Ghosh, P., Han, G., De, M., Kim, C. K. & Rotello, V. M. Gold nanoparticles in delivery applications. Adv. Drug Deliv. Rev. 60, 1307–1315 (2008).

    Article  CAS  Google Scholar 

  113. Aznar, E. et al. pH- and photo-switched release of guest molecules from mesoporous silica supports. J. Am. Chem. Soc. 131, 6833–6843 (2009).

    Article  CAS  Google Scholar 

  114. Kang, H. et al. Near-infrared light-responsive core-shell nanogels for targeted drug delivery. ACS Nano 5, 5094–5099 (2011).

    Article  CAS  Google Scholar 

  115. Lee, J., Park, H. & Kim, W. J. Nano ‘chocolate waffle’ for near-IR responsive drug releasing system. Small 11, 5315–5323 (2015).

    Article  CAS  Google Scholar 

  116. Tang, Y. et al. An aptamer-targeting photoresponsive drug delivery system using ‘off–on’ graphene oxide wrapped mesoporous silica nanoparticles. Nanoscale 7, 6304–6310 (2015).

    Article  CAS  Google Scholar 

  117. Cobley, C. M., Au, L., Chen, J. & Xia, Y. Targeting gold nanocages to cancer cells for photothermal destruction and drug delivery. Expert Opin. Drug Deliv. 7, 577–587 (2010).

    Article  CAS  Google Scholar 

  118. Hribar, K. C., Lee, M. H., Lee, D. & Burdick, J. A. Enhanced release of small molecules from near-infrared light responsive polymer-nanorod composites. ACS Nano 5, 2948–2956 (2011).

    Article  CAS  Google Scholar 

  119. Niidome, T. et al. PEG-modified gold nanorods with a stealth character for in vivo applications. J. Control. Release 114, 343–347 (2006).

    Article  CAS  Google Scholar 

  120. MacLeod, M. J. & Johnson, J. A. PEGylated N-heterocyclic carbene anchors designed to stabilize gold nanoparticles in biologically relevant media. J. Am. Chem. Soc. 137, 7974–7977 (2015).

    Article  CAS  Google Scholar 

  121. Li, W. et al. Remote modulation of neural activities via near-infrared triggered release of biomolecules. Biomaterials 65, 76–85 (2015).

    Article  CAS  Google Scholar 

  122. Yu, H. et al. pH- and NIR light-responsive micelles with hyperthermia-triggered tumor penetration and cytoplasm drug release to reverse doxorubicin resistance in breast cancer. Adv. Funct. Mater. 25, 2489–2500 (2015).

    Article  CAS  Google Scholar 

  123. Sherlock, S. P., Tabakman, S. M., Xie, L. & Dai, H. Photothermally enhanced drug delivery by ultrasmall multifunctional FeCo/graphitic shell nanocrystals. ACS Nano 5, 1505–1512 (2011).

    Article  CAS  Google Scholar 

  124. Chen, W. et al. Black phosphorus nanosheet-based drug delivery system for synergistic photodynamic/photothermal/chemotherapy of cancer. Adv. Mater. 29, 1603864 (2017).

    Article  CAS  Google Scholar 

  125. Kim, H. et al. Visible light-triggered on-demand drug release from hybrid hydrogels and its application in transdermal patches. Adv. Healthc. Mater. 4, 2071–2077 (2015).

    Article  CAS  Google Scholar 

  126. Bonnett, R. Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy. Chem. Soc. Rev. 24, 19 (1995).

    Article  CAS  Google Scholar 

  127. Ackroyd, R., Kelty, C., Brown, N. & Reed, M. The history of photodetection and photodynamic therapy. Photochem. Photobiol. 74, 656 (2001).

    Article  CAS  Google Scholar 

  128. Bio, M. et al. Site-specific and far-red-light-activatable prodrug of combretastatin A-4 using photo-unclick chemistry. J. Med. Chem. 56, 3936–3942 (2013).

    Article  CAS  Google Scholar 

  129. Hossion, A. M. L., Bio, M., Nkepang, G., Awuah, S. G. & You, Y. Visible light controlled release of anticancer drug through double activation of prodrug. ACS Med. Chem. Lett. 4, 124–127 (2013).

    Article  CAS  Google Scholar 

  130. Ke, M.-R. et al. A tumor-targeted activatable phthalocyanine-tetrapeptide-doxorubicin conjugate for synergistic chemo-photodynamic therapy. Eur. J. Med. Chem. 127, 200–209 (2017).

    Article  CAS  Google Scholar 

  131. Rwei, A. Y. et al. Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes. Proc. Natl Acad. Sci. USA 112, 15719–15724 (2015).

    CAS  Google Scholar 

  132. Berg, K. & Moan, J. Lysosomes as photochemical targets. Int. J. Cancer 59, 814–822 (1994).

    Article  CAS  Google Scholar 

  133. Berg, K. et al. Photochemical Internalization: a novel technique for delivery of macromolecules into cytosol. Cancer Res. 59, 1180–1183 (1999).

    CAS  Google Scholar 

  134. Selbo, P. K. et al. Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules. J. Control. Release 148, 2–12 (2010).

    Article  CAS  Google Scholar 

  135. Nishiyama, N. et al. Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer. Nat. Mater. 4, 934–941 (2005).

    Article  CAS  Google Scholar 

  136. Carter, K. A. et al. Porphyrin-phospholipid liposomes permeabilized by near-infrared light. Nat. Commun. 5, 3546 (2014).

    Article  CAS  Google Scholar 

  137. Luo, D. et al. Porphyrin-phospholipid liposomes with tunable leakiness. J. Control. Release 220, 484–494 (2015).

    Article  CAS  Google Scholar 

  138. DeForest, C. A. & Anseth, K. S. Advances in bioactive hydrogels to probe and direct cell fate. Annu. Rev. Chem. Biomol. Eng. 3, 421–444 (2012).

    Article  CAS  Google Scholar 

  139. Fairbanks, B. D., Schwartz, M. P., Bowman, C. N. & Anseth, K. S. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials 30, 6702–6707 (2009).

    Article  CAS  Google Scholar 

  140. Hahn, M. S., Miller, J. S. & West, J. L. Three-dimensional biochemical and biomechanical patterning of hydrogels for guiding cell behavior. Adv. Mater. 18, 2679–2684 (2006). This study demonstrates physiochemical photopatterning within hydrogel biomaterials.

    Article  CAS  Google Scholar 

  141. Lee, S.-H. H., Moon, J. J. & West, J. L. Three-dimensional micropatterning of bioactive hydrogels via two-photon laser scanning photolithography for guided 3D cell migration. Biomaterials 29, 2962–2968 (2008).

    Article  CAS  Google Scholar 

  142. Hoffmann, J. C. & West, J. L. Three-dimensional photolithographic patterning of multiple bioactive ligands in poly(ethylene glycol) hydrogels. Soft Matter 6, 5056–5063 (2010).

    Article  CAS  Google Scholar 

  143. Hahn, M. S. et al. Photolithographic patterning of polyethylene glycol hydrogels. Biomaterials 27, 2519–2524 (2006).

    Article  CAS  Google Scholar 

  144. DeLong, S. A., Moon, J. J. & West, J. L. Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. Biomaterials 26, 3227–3234 (2005).

    Article  CAS  Google Scholar 

  145. Culver, J. C. et al. Three-dimensional biomimetic patterning in hydrogels to guide cellular organization. Adv. Mater. 24, 2344–2348 (2012).

    Article  CAS  Google Scholar 

  146. Moon, J. J., Hahn, M. S., Kim, I., Nsiah, B. A. & West, J. L. Micropatterning of poly(ethylene glycol) diacrylate hydrogels with biomolecules to regulate and guide endothelial morphogenesis. Tissue Eng. Part A 15, 579–585 (2009).

    Article  CAS  Google Scholar 

  147. Leslie-Barbick, J. E., Shen, C., Chen, C. & West, J. L. Micron-scale spatially patterned, covalently immobilized vascular endothelial growth factor on hydrogels accelerates endothelial tubulogenesis and increases cellular angiogenic responses. Tissue Eng. Part A 17, 221–229 (2011).

    Article  CAS  Google Scholar 

  148. Luo, Y. & Shoichet, M. S. A photolabile hydrogel for guided three-dimensional cell growth and migration. Nat. Mater. 3, 249–253 (2004).

    Article  CAS  Google Scholar 

  149. Wosnick, J. H. & Shoichet, M. S. Three-dimensional chemical patterning of transparent hydrogels. Chem. Mater. 20, 55–60 (2008).

    Article  CAS  Google Scholar 

  150. Wylie, R. G. et al. Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. Nat. Mater. 10, 799–806 (2011). This study describes the strategy to simultaneously immobilize multiple proteins within a synthetic cell culture platform.

    Article  CAS  Google Scholar 

  151. Wylie, R. G. & Shoichet, M. S. Three-dimensional spatial patterning of proteins in hydrogels. Biomacromolecules 12, 3789–3796 (2011).

    Article  CAS  Google Scholar 

  152. Luo, Y. & Shoichet, M. S. Light-activated immobilization of biomolecules to agarose hydrogels for controlled cellular response. Biomacromolecules 5, 2315–2323 (2004).

    Article  CAS  Google Scholar 

  153. Polizzotti, B. D., Fairbanks, B. D. & Anseth, K. S. Three-dimensional biochemical patterning of click-based composite hydrogels via thiolene photopolymerization. Biomacromolecules 9, 1084–1087 (2008).

    Article  CAS  Google Scholar 

  154. Adzima, B. J. et al. Spatial and temporal control of the alkyne-azide cycloaddition by photoinitiated Cu(II) reduction. Nat. Chem. 3, 258–261 (2011).

    Article  CAS  Google Scholar 

  155. 155. Bryant, S. J., Nuttelman, C. R. & Anseth, K. S. Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro. J. Biomater. Sci. Ed. 11, 439–457 (2000).

    Article  CAS  Google Scholar 

  156. DeForest, C. A. & Anseth, K. S. Cytocompatible click-based hydrogels with dynamically tunable properties through orthogonal photocoupling and photodegradation reactions. Nat. Chem. 3, 925–931 (2011).

    Article  CAS  Google Scholar 

  157. Hoyle, C. E. & Bowman, C. N. Thiol-ene click chemistry. Angew. Chem. Int. Ed. 49, 1540–1573 (2010).

    Article  CAS  Google Scholar 

  158. DeForest, C. A., Polizzotti, B. D. & Anseth, K. S. Sequential click reactions for synthesizing and patterning three-dimensional cell microenvironments. Nat. Mater. 8, 659–664 (2009).

    Article  CAS  Google Scholar 

  159. DeForest, C. A., Sims, E. A. & Anseth, K. S. Peptide-functionalized click hydrogels with independently tunable mechanics and chemical functionality for 3D cell culture. Chem. Mater. 22, 4783–4790 (2010).

    Article  CAS  Google Scholar 

  160. Sawicki, L. A. & Kloxin, A. M. Design of thiol-ene photoclick hydrogels using facile techniques for cell culture applications. Biomater. Sci. 2, 1612–1626 (2014).

    Article  CAS  Google Scholar 

  161. Fairbanks, B. D. et al. A versatile synthetic extracellular matrix mimic via thiol-norbornene photopolymerization. Adv. Mater. 21, 5005–5010 (2009).

    Article  CAS  Google Scholar 

  162. Alge, D. L., Azagarsamy, M. A., Donohue, D. F. & Anseth, K. S. Synthetically tractable click hydrogels for three-dimensional cell culture formed using tetrazine-norbornene chemistry. Biomacromolecules 14, 949–953 (2013).

    Article  CAS  Google Scholar 

  163. Gramlich, W. M., Kim, I. L. & Burdick, J. A. Synthesis and orthogonal photopatterning of hyaluronic acid hydrogels with thiol-norbornene chemistry. Biomaterials 34, 9803–9811 (2013).

    Article  CAS  Google Scholar 

  164. Wade, R. J., Bassin, E. J., Gramlich, W. M. & Burdick, J. A. Nanofibrous hydrogels with spatially patterned biochemical signals to control cell behavior. Adv. Mater. 27, 1356–1362 (2015).

    Article  CAS  Google Scholar 

  165. Mosiewicz, K. A. et al. In situ cell manipulation through enzymatic hydrogel photopatterning. Nat. Mater. 12, 1071–1077 (2013).

    Article  CAS  Google Scholar 

  166. Griffin, D. R. et al. Hybrid photopatterned enzymatic reaction (HyPER) for in situ cell manipulation. ChemBioChem 15, 233–242 (2014).

    Article  CAS  Google Scholar 

  167. Petersen, S. et al. Phototriggering of cell adhesion by caged cyclic RGD peptides. Angew. Chem. Int. Ed. 120, 3236–3239 (2008).

    Article  Google Scholar 

  168. Ohmuro-Matsuyama, Y. & Tatsu, Y. Photocontrolled cell adhesion on a surface functionalized with a caged arginine-glycine-aspartate peptide. Angew. Chem. Int. Ed. 47, 7527–7529 (2008).

    Article  CAS  Google Scholar 

  169. Weis, S., Lee, T. T., del Campo, A. & García, A. J. Dynamic cell-adhesive microenvironments and their effect on myogenic differentiation. Acta Biomater. 9, 8059–8066 (2013).

    Article  CAS  Google Scholar 

  170. Lee, T. T. et al. Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat. Mater 14, 352–360 (2015). This study describes a powerful example in which biomaterial photomodification, including spatial patterning, is performed in vivo.

    Article  CAS  Google Scholar 

  171. Kloxin, A. M., Kasko, A. M., Salinas, C. N. & Anseth, K. S. Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science 324, 59–63 (2009). A demonstration of cytocompatible biomaterial photodegradation.

    Article  CAS  Google Scholar 

  172. Griffin, D. R. & Kasko, A. M. Photodegradable macromers and hydrogels for live cell encapsulation and release. J. Am. Chem. Soc. 134, 13103–13107 (2012).

    Article  CAS  Google Scholar 

  173. Azagarsamy, M. A. & Anseth, K. S. Wavelength-controlled photocleavage for the orthogonal and sequential release of multiple proteins. Angew. Chem. Int. Ed. 52, 13803–13807 (2013).

    Article  CAS  Google Scholar 

  174. DeForest, C. A. & Anseth, K. S. Photoreversible patterning of biomolecules within click-based hydrogels. Angew. Chem. Int. Ed. 51, 1816–1819 (2011).

    Article  CAS  Google Scholar 

  175. Gandavarapu, N. R., Azagarsamy, M. A. & Anseth, K. S. Photo-click living strategy for controlled, reversible exchange of biochemical ligands. Adv. Mater. 26, 2521–2526 (2014).

    Article  CAS  Google Scholar 

  176. DeForest, C. A. & Tirrell, D. A. A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nat. Mater. 14, 523–531 (2015). This study depicts a powerful approach to reversibly modify hydrogels with full-length proteins in the presence of live cells.

    Article  CAS  Google Scholar 

  177. Farahani, P. E., Adelmund, S. M., Shadish, J. A. & DeForest, C. A. Photomediated oxime ligation as a bioorthogonal tool for spatiotemporally-controlled hydrogel formation and modification. J. Mater. Chem. B 5, 4435–4442 (2017).

    Article  CAS  Google Scholar 

  178. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  CAS  Google Scholar 

  179. Reilly, G. C. & Engler, A. J. Intrinsic extracellular matrix properties regulate stem cell differentiation. J. Biomech. 43, 55–62 (201§0).

  180. Janmey, P. A. & Miller, R. T. Mechanisms of mechanical signaling in development and disease. J. Cell Sci. 124, 9–18 (2011).

    Article  CAS  Google Scholar 

  181. Nemir, S., Hayenga, H. N. & West, J. L. PEGDA hydrogels with patterned elasticity: novel tools for the study of cell response to substrate rigidity. Biotechnol. Bioeng. 105, 636–644 (2010).

    Article  CAS  Google Scholar 

  182. Guvendiren, M., Perepelyuk, M., Wells, R. G. & Burdick, J. A. Hydrogels with differential and patterned mechanics to study stiffness-mediated myofibroblastic differentiation of hepatic stellate cells. J. Mech. Behav. Biomed. Mater. 38, 198–208 (2014).

    Article  CAS  Google Scholar 

  183. Nowatzki, P. J., Franck, C., Maskarinec, S. A., Ravichandran, G. & Tirrell, D. A. Mechanically tunable thin films of photosensitive artificial proteins: preparation and characterization by nanoindentation. Macromolecules 41, 1839–1845 (2008).

    Article  CAS  Google Scholar 

  184. Khetan, S., Katz, J. S. & Burdick, J. A. Sequential crosslinking to control cellular spreading in 3-dimensional hydrogels. Soft Matter 5, 1601–1606 (2009).

    Article  CAS  Google Scholar 

  185. Khetan, S. & Burdick, J. A. Patterning network structure to spatially control cellular remodeling and stem cell fate within 3-dimensional hydrogels. Biomaterials 31, 8228–8234 (2010).

    Article  CAS  Google Scholar 

  186. Khetan, S. et al. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12, 458–465 (2013). This study describes the on-demand material crosslinking used to reveal the importance of matrix interactions for stem cell differentiation.

    Article  CAS  Google Scholar 

  187. Liu, Z. et al. Spatiotemporally controllable and cytocompatible approach builds 3D cell culture matrix by photo-uncaged-thiol michael addition reaction. Adv. Mater. 26, 3912–3917 (2014).

    Article  CAS  Google Scholar 

  188. Mosiewicz, K. A., Kolb, L., Van Der Vlies, A. J. & Lutolf, M. P. Microscale patterning of hydrogel stiffness through light-triggered uncaging of thiols. Biomater. Sci. 2, 1640–1651 (2014).

    Article  CAS  Google Scholar 

  189. Cui, J., Wang, M., Zheng, Y., Rodríguez Muñiz, G. M. & del Campo, A. Light-triggered cross-linking of alginates with caged Ca2+. Biomacromolecules 14, 1251–1256 (2013).

    Article  CAS  Google Scholar 

  190. Stowers, R. S., Allen, S. C. & Suggs, L. J. Dynamic phototuning of 3D hydrogel stiffness. Proc. Natl Acad. Sci. USA 112, 1953–1958 (2015).

    Article  CAS  Google Scholar 

  191. Brandenberg, N. & Lutolf, M. P. In situ patterning of microfluidic networks in 3D cell-laden hydrogels. Adv. Mater. 28, 7450–7456 (2016).

    Article  CAS  Google Scholar 

  192. Heintz, K. A. et al. Fabrication of 3D biomimetic microfluidic networks in hydrogels. Adv. Healthc. Mater. 5, 2153–2160 (2016).

    Article  CAS  Google Scholar 

  193. Berkovitch, Y., Yelin, D. & Seliktar, D. Photo-patterning PEG-based hydrogels for neuronal engineering. Eur. Polym. J. 72, 473–483 (2015).

    Article  CAS  Google Scholar 

  194. Johnson, J. A., Finn, M. G., Koberstein, J. T. & Turro, N. J. Synthesis of photocleavable linear macromonomers by ATRP and star macromonomers by a tandem ATRP-click reaction: precursors to photodegradable model networks. Macromolecules 40, 3589–3598 (2007).

    Article  CAS  Google Scholar 

  195. Kloxin, A. M., Tibbitt, M. W. & Anseth, K. S. Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms. Nat. Protoc. 5, 1867–1887 (2010).

    Article  CAS  Google Scholar 

  196. Johnson, J. A., Baskin, J. M., Bertozzi, C. R., Koberstein, J. T. & Turro, N. J. Copper-free click chemistry for the in situ crosslinking of photodegradable star polymers. Chem. Commun. 0, 3064–3066 (2008).

    Article  CAS  Google Scholar 

  197. Wong, D. Y., Griffin, D. R., Reed, J. & Kasko, A. M. Photodegradable hydrogels to generate positive and negative features over multiple length scales. Macromolecules 43, 2824–2831 (2010).

    Article  CAS  Google Scholar 

  198. Frey, M. T. & Wang, Y. L. A photo-modulatable material for probing cellular responses to substrate rigidity. Soft Matter 5, 1918–1924 (2009).

    Article  CAS  Google Scholar 

  199. Tsang, K. M. C. et al. Facile one-step micropatterning using photodegradable gelatin hydrogels for improved cardiomyocyte organization and alignment. Adv. Funct. Mater. 25, 977–986 (2015).

    Article  CAS  Google Scholar 

  200. Kirschner, C. M. & Anseth, K. S. In situ control of cell substrate microtopographies using photolabile hydrogels. Small 9, 578–584 (2013).

    Article  CAS  Google Scholar 

  201. Kloxin, A. M., Tibbitt, M. W., Kasko, A. M., Fairbairn, J. a & Anseth, K. S. Tunable hydrogels for external manipulation of cellular microenvironments through controlled photodegradation. Adv. Mater. 22, 61–66 (2010).

    Article  CAS  Google Scholar 

  202. Tibbitt, M. W., Kloxin, A. M., Dyamenahalli, K. U. & Anseth, K. S. Controlled two-photon photodegradation of PEG hydrogels to study and manipulate subcellular interactions on soft materials. Soft Matter 6, 5100–5108 (2010).

    Article  CAS  Google Scholar 

  203. Kloxin, A. M., Benton, J. A. & Anseth, K. S. In situ elasticity modulation with dynamic substrates to direct cell phenotype. Biomaterials 31, 1–8 (2010).

    Article  CAS  Google Scholar 

  204. Wang, H., Haeger, S. M., Kloxin, A. M., Leinwand, L. A. & Anseth, K. S. Redirecting valvular myofibroblasts into dormant fibroblasts through light-mediated reduction in substrate modulus. PLoS ONE 7, e39969 (2012).

    Article  CAS  Google Scholar 

  205. Yang, C., Tibbitt, M. W., Basta, L. & Anseth, K. S. Mechanical memory and dosing influence stem cell fate. Nat. Mater. 13, 645–652 (2014).

    Article  CAS  Google Scholar 

  206. Tibbitt, M. W., Kloxin, A. M., Sawicki, L. A. & Anseth, K. S. Mechanical properties and degradation of chain and step-polymerized photodegradable hydrogels. Macromolecules 46, 2785–2792 (2013).

    Article  CAS  Google Scholar 

  207. McKinnon, D. D., Brown, T. E., Kyburz, K. A., Kiyotake, E. & Anseth, K. S. Design and characterization of a synthetically accessible, photodegradable hydrogel for user-directed formation of neural networks. Biomacromolecules 15, 2808–2816 (2014).

    Article  CAS  Google Scholar 

  208. Arakawa, C. K., Badeau, B. A., Zheng, Y. & Deforest, C. A. Multicellular vascularized engineered tissues through user-programmable biomaterial photodegradation. Adv. Mater. 29, 1703156 (2017).

    Article  CAS  Google Scholar 

  209. Bernard, A. B., Lin, C.-C. C. & Anseth, K. S. A microwell cell culture platform for the aggregation of pancreatic beta-cells. Tissue Eng. Part C Methods 18, 583–592 (2012).

    Article  CAS  Google Scholar 

  210. Lewis, K. J. R. et al. In vitro model alveoli from photodegradable microsphere templates. Biomater. Sci. 3, 821–832 (2015).

    Article  CAS  Google Scholar 

  211. Kloxin, A. M. et al. Responsive culture platform to examine the influence of microenvironmental geometry on cell function in 3D. Integr. Biol. 4, 1540–1549 (2012).

    Article  CAS  Google Scholar 

  212. Fairbanks, B. D., Singh, S. P., Bowman, C. N. & Anseth, K. S. Photodegradable, photoadaptable hydrogels via radical-mediated disulfide fragmentation reaction. Macromolecules 44, 2444–2450 (2011).

    Article  CAS  Google Scholar 

  213. Tamura, M. et al. Optical cell separation from three-dimensional environment in photodegradable hydrogels for pure culture techniques. Sci. Rep. 4, 4793 (2014).

    Article  CAS  Google Scholar 

  214. Truong, V. X. et al. Photodegradable gelatin-based hydrogels prepared by bioorthogonal click chemistry for cell encapsulation and release. Biomacromolecules 16, 2246–2253 (2015).

    Article  CAS  Google Scholar 

  215. Ki, C. S., Shih, H. & Lin, C. C. Facile preparation of photodegradable hydrogels by photopolymerization. Polymer 54, 2115–2122 (2013).

    Article  CAS  Google Scholar 

  216. Zhu, C. C. & Bettinger, C. J. Light-induced remodeling of physically crosslinked hydrogels using near-IR wavelengths. J. Mater. Chem. B 2, 1613–1618 (2014).

    Article  CAS  Google Scholar 

  217. Azagarsamy, M. A., McKinnon, D. D., Age, D. L. & Anseth, K. S. Coumarin-based photodegradable hydrogel: design, synthesis, gelation, and degradation kinetics. ACS Macro Lett. 3, 515–519 (2014).

    Article  CAS  Google Scholar 

  218. Andreopoulos, F. M. et al. Photoscissable hydrogel synthesis via rapid photopolymerization of novel PEG-based polymers in the absence of photoinitiators. J. Am. Chem. Soc. 118, 6235–6240 (1996).

    Article  CAS  Google Scholar 

  219. Andreopoulos, F. M., Beckman, E. J. & Russell, A. J. Light-induced tailoring of PEG-hydrogel properties. Biomaterials 19, 1343–1352 (1998).

    Article  CAS  Google Scholar 

  220. Andreopoulos, F. M., Beckman, E. J. & Russell, A. J. Photoswitchable PEG-CA hydrogels and factors that affect their photosensitivity. J. Polym. Sci. Part A Polym. Chem. 38, 1466–1476 (2000).

    Article  CAS  Google Scholar 

  221. Zheng, Y. et al. A novel photoscissile poly(ethylene glycol)-based hydrogel. Adv. Funct. Mater. 11, 37–40 (2001).

    Article  CAS  Google Scholar 

  222. Zheng, Y. J. et al. PEG-based hydrogel synthesis via the photodimerization of anthracene groups. Macromolecules 35, 5228–5234 (2002).

    Article  CAS  Google Scholar 

  223. Sako, Y. & Takaguchi, Y. A photo-responsive hydrogelator having gluconamides at its peripheral branches. Org. Biomol. Chem. 6, 3843–3847 (2008).

    Article  CAS  Google Scholar 

  224. Chen, Y. & Geh, J. L. Copolymers derived from 7-acryloyloxy-4-methylcoumarin and acrylates: 2. Reversible photocrosslinking and photocleavage. Polymer 37, 4481–4486 (1996).

    Article  CAS  Google Scholar 

  225. Maddipatla, M. V. S. N. et al. Photoresponsive coumarin polyesters that exhibit cross-linking and chain scission properties. Macromolecules 46, 5133–5140 (2013).

    Article  CAS  Google Scholar 

  226. Tamesue, S., Takashima, Y., Yamaguchi, H., Shinkai, S. & Harada, A. Photoswitchable supramolecular hydrogels formed by cyclodextrins and azobenzene polymers. Angew. Chem. Int. Ed. 49, 7461–7464 (2010).

    Article  CAS  Google Scholar 

  227. Rosales, A. M., Mabry, K. M., Nehls, E. M. & Anseth, K. S. Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels. Biomacromolecules 16, 798–806 (2015).

    Article  CAS  Google Scholar 

  228. Rape, A. D., Zibinsky, M., Murthy, N. & Kumar, S. A synthetic hydrogel for the high-throughput study of cell–ECM interactions. Nat. Commun. 6, 8129 (2015).

    Article  Google Scholar 

  229. Smith, D. J. et al. A multiphase transitioning peptide hydrogel for suturing ultrasmall vessels. Nat. Nanotechnol. 11, 95–102 (2016).

    Article  CAS  Google Scholar 

  230. Sharma, B. et al. Human cartilage repair with a photoreactive adhesive-hydrogel composite. Sci. Transl. Med. 5, 167ra6 (2013).

    Article  CAS  Google Scholar 

  231. San Miguel, V., Bochet, C. G. & del Campo, A. Wavelength-selective caged surfaces: how many functional levels are possible? J. Am. Chem. Soc. 133, 5380–5388 (2011).

    Article  CAS  Google Scholar 

  232. Brown, T. E., Marozas, I. A. & Anseth, K. S. Amplified photodegradation of cell-laden hydrogels via an addition-fragmentation chain transfer reaction. Adv. Mater. 29, 1605001 (2017).

    Article  CAS  Google Scholar 

  233. Zhao, Y.-L. & Stoddart, J. F. Azobenzene-based light-responsive hydrogel system. Langmuir 25, 8442–8446 (2009).

    Article  CAS  Google Scholar 

  234. Wang, D., Wagner, M., Butt, H.-J. & Wu, S. Supramolecular hydrogels constructed by red-light-responsive host–guest interactions for photo-controlled protein release in deep tissue. Soft Matter 11, 7656–7662 (2015).

    Article  CAS  Google Scholar 

  235. Schindler, S. E. et al. Photo-activatable Cre recombinase regulates gene expression in vivo. Sci. Rep 5, 13627 (2015).

    Article  Google Scholar 

  236. Kawano, F., Okazaki, R., Yazawa, M. & Sato, M. A photoactivatable Cre–loxP recombination system for optogenetic genome engineering. Nat. Chem. Biol. 12, 1059–1064 (2016).

    Article  CAS  Google Scholar 

  237. Nihongaki, Y., Kawano, F., Nakajima, T. & Sato, M. Photoactivatable CRISPR-Cas9 for optogenetic genome editing. Nat. Biotechnol. 33, 755–760 (2015).

    Article  CAS  Google Scholar 

  238. Nihongaki, Y., Furuhata, Y., Otabe, T., Hasegawa, Saki Yoshimoto, K. & Sato, M. CRISPR-Cas9-based photoactivatable transcription systems to induce neuronal differentiation. Nat. Methods 14, 963–966 (2017).

    Article  CAS  Google Scholar 

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Acknowledgements

C.A.D. gratefully acknowledges support in the form of a faculty early career development (CAREER) award from the National Science Foundation (DMR-1652141), an innovation pilot award from the Institute of Stem Cell & Regenerative Medicine and a royalty research grant (A112554) from the University of Washington.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA

    Emily R. Ruskowitz & Cole A. DeForest

  2. Department of Bioengineering, University of Washington, Seattle, WA 98105, USA

    Cole A. DeForest

  3. Institute of Stem Cell & Regenerative Medicine, University of Washington, Seattle, WA 98109, USA

    Cole A. DeForest

  4. Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA 98195, USA

    Cole A. DeForest

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  1. Emily R. Ruskowitz
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  2. Cole A. DeForest
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All authors contributed equally to the preparation of this manuscript.

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Correspondence to Cole A. DeForest.

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The authors declare no competing interests.

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Ruskowitz, E., DeForest, C. Photoresponsive biomaterials for targeted drug delivery and 4D cell culture. Nat Rev Mater 3, 17087 (2018). https://doi.org/10.1038/natrevmats.2017.87

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