Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Polymer encapsulation of ruthenium complexes for biological and medicinal applications

Abstract

Some Ru complexes have extremely promising anticancer or antibacterial properties, but the poor H2O solubility and/or low stability of many Ru complexes in aqueous solution under physiological conditions and/or metabolic or biodistribution profiles prevent their therapeutic use. To overcome these drawbacks, various strategies have been developed to improve the delivery of these compounds to their target tissues. The first strategy is based on physical encapsulation of Ru complexes in carriers, such as polymeric micelles, microparticles, nanoparticles and polymer–lipid hybrids, which enables the delivery and controlled release of the active Ru drug candidate. The second strategy involves covalent conjugation of the Ru complex to a polymer to give a prodrug that can be converted into the active drug at a more controllable rate. In this Review, we provide an overview of recent developments in polymer encapsulation of Ru complexes for biological and medicinal applications. We place particular emphasis on how polymer structure affects Ru delivery.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Representative Ru complexes with medicinal potential.
Fig. 2: Methods to encapsulate Ru complexes in polymers.
Fig. 3: Some prominent biodegradable polymers.
Fig. 4: Synthetic strategies for Ru-conjugated polymer prodrug candidates.
Fig. 5: Photoactivatable nanocarriers.
Fig. 6: Ru–polymer conjugates can be activated either by biodegradation or light.
Fig. 7: Synthesis of Ru complexes bearing ligands with 2–6 polymer chains.

Similar content being viewed by others

References

  1. Grimley, B. & Lansing, E. The inhibition of growth or cell division in Escherichia by different ionic species of platinum(iv) complexes. J. Biol. Chem. 242, 1347–1352 (1967).

    PubMed  Google Scholar 

  2. Galluzzi, L. et al. Molecular mechanisms of cisplatin resistance. Oncogene 31, 1869–1883 (2012).

    CAS  PubMed  Google Scholar 

  3. Poynton, F. E. et al. The development of ruthenium polypyridyl complexes and conjugates for in vitro cellular and in vivo applications. Chem. Soc. Rev. 46, 5771–5804 (2017).

    Google Scholar 

  4. Notaro, A. & Gasser, G. Monomeric and dimeric coordinatively saturated and substitutionally inert Ru polypyridyl complexes as anticancer drug candidates. Chem. Soc. Rev. 46, 7317–7337 (2017).

    CAS  PubMed  Google Scholar 

  5. Antonarakis, E. S. & Emadi, A. Ruthenium-based chemotherapeutics: are they ready for prime time? Cancer Chemother. Pharmacol. 66, 1–9 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Levina, A., Mitra, A. & Lay, P. A. Recent developments in ruthenium anticancer drugs. Metallomics 1, 458–470 (2009).

    CAS  PubMed  Google Scholar 

  7. Kostova, I. Ruthenium complexes as anticancer agents. Curr. Med. Chem. 13, 1085–1107 (2006).

    CAS  PubMed  Google Scholar 

  8. Li, F., Collins, J. G. & Keene, F. R. Ruthenium complexes as antimicrobial agents. Chem. Soc. Rev. 44, 2529–2542 (2015).

    CAS  PubMed  Google Scholar 

  9. Meggers, E. From conventional to unusual enyzme inhibitor scaffolds: the quest for target specificity. Angew. Chem. Int. Ed. 50, 2442–2448 (2011).

    CAS  Google Scholar 

  10. Meggers, E. Targeting proteins with metal complexes. Chem. Commun. 7, 1001–1010 (2009).

    Google Scholar 

  11. Kilpin, K. J. & Dyson, P. J. Enzyme inhibition by metal complexes: concepts, strategies and applications. Chem. Sci. 4, 1410–1419 (2013).

    CAS  Google Scholar 

  12. Mari, C., Pierroz, V., Ferrari, S. & Gasser, G. Combination of Ru complexes and light: new frontiers in cancer therapy. Chem. Sci. 6, 2660–2686 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Heinemann, F., Karges, J. & Gasser, G. Critical overview of the use of Ru(ii) polypyridyl complexes as photosensitizers in one-photon and two-photon photodynamic therapy. Acc. Chem. Res. 50, 2727–2736 (2017).

    CAS  PubMed  Google Scholar 

  14. Knoll, J. D. & Turro, C. Control and utilization of ruthenium and rhodium metal complex excited states for photoactivated cancer therapy. Coord. Chem. Rev. 282–283, 110–126 (2015).

    PubMed  PubMed Central  Google Scholar 

  15. Shi, G. et al. Ru(ii) dyads derived from α-oligothiophenes: a new class of potent and versatile photosensitizers for PDT. Coord. Chem. Rev. 282–283, 127–138 (2015).

    Google Scholar 

  16. Monro, S. et al. Transition metal complexes and photodynamic therapy from a tumor-centered approach: challenges, opportunities, and highlights from the development of TLD1433. Chem. Rev. 119, 797–828 (2019).

    CAS  Google Scholar 

  17. Bastos, C. M., Gordon, K. A. & Ocain, T. D. Synthesis and immunosuppressive activity of ruthenium complexes. Bioorg. Med. Chem. Lett. 8, 147–150 (1998).

    CAS  PubMed  Google Scholar 

  18. Gill, M. R. & Thomas, J. A. Ruthenium(ii) polypyridyl complexes and DNA—from structural probes to cellular imaging and therapeutics. Chem. Soc. Rev. 41, 3179–3192 (2012).

    CAS  PubMed  Google Scholar 

  19. Puckett, C. A., Ernst, R. J. & Barton, J. K. Exploring the cellular accumulation of metal complexes. Dalton Trans. 39, 1159–1170 (2010).

    CAS  PubMed  Google Scholar 

  20. Boynton, A. N., Marce, L. & Barton, J. K. [Ru(Me4phen)2dppz]2+, a light switch for dna mismatches. J. Am. Chem. Soc. 138, 5020–5023 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Martí, A. A. et al. Inorganic–organic hybrid luminescent binary probe for DNA detection based on spin-forbidden resonance energy transfer. J. Am. Chem. Soc. 129, 8680–8681 (2007).

    PubMed  PubMed Central  Google Scholar 

  22. Dwyer, F. P., Gyarfas, E. C., Rogers, W. P. & Koch, J. H. Biological activity of complex ions. Nature 170, 190–191 (1952).

    CAS  PubMed  Google Scholar 

  23. Clarke, M. J. Oncological implications of the chemistry of ruthenium. Met. Ions. Biol. Syst. 11, 231–283 (1980).

    CAS  Google Scholar 

  24. Allardyce, C. S. & Dyson, P. J. Ruthenium in medicine: current clinical uses and future prospects. Platin. Met. Rev. 45, 62–69 (2001).

    CAS  Google Scholar 

  25. Allardyce, C. S., Dorcier, A., Scolaro, C. & Dyson, P. J. Development of organometallic (organo-transition metal) pharmaceuticals. Appl. Organomet. Chem. 19, 1–10 (2005).

    CAS  Google Scholar 

  26. Clarke, M. J. Ruthenium metallopharmaceuticals. Coord. Chem. Rev. 232, 69–93 (2002).

    CAS  Google Scholar 

  27. Schluga, P. et al. Redox behavior of tumor-inhibiting ruthenium(iii) complexes and effects of physiological reductants on their binding to GMP. Dalton Trans. 14, 1796–1802 (2006).

    Google Scholar 

  28. Henning, T., Kraus, M., Brischwein, M., Otto, A. M. & Wolf, B. Relevance of tumor microenvironment for progression, therapy and drug development. Anticancer Drugs 15, 7–14 (2004).

    CAS  PubMed  Google Scholar 

  29. Reisner, E., Arion, V. B., Keppler, B. K. & Pombeiro, A. J. L. Electron-transfer activated metal-based anticancer drugs. Inorg. Chim. Acta 361, 1569–1583 (2008).

    CAS  Google Scholar 

  30. Clarke, M. J., Bitier, S., Rennert, D. & Buchbinder, M. Reduction and subsequent binding of ruthenium ions catalyzed by subcellular components. J. Inorg. Biochem. 12, 79–87 (1980).

    CAS  PubMed  Google Scholar 

  31. Allardyce, C. S., Dyson, P. J., Ellis, D. J. & Heath, S. L. [Ru(η6-p-cymene)Cl2(pta)] (pta=1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane): a water soluble compound that exhibits pH dependent DNA binding providing selectivity for diseased cells. Chem. Commun. 2, 1396–1397 (2001).

    Google Scholar 

  32. Scolaro, C. et al. In vitro and in vivo evaluation of ruthenium(ii)-arene PTA complexes. J. Med. Chem. 48, 4161–4171 (2005).

    CAS  PubMed  Google Scholar 

  33. Bergamo, A. et al. Modulation of the metastatic progression of breast cancer with an organometallic ruthenium compound. Int. J. Oncol. 33, 1281–1289 (2008).

    CAS  PubMed  Google Scholar 

  34. Aird, R. E. et al. In vitro and in vivo activity and cross resistance profiles of novel ruthenium(ii) organometallic arene complexes in human ovarian cancer. Br. J. Cancer 86, 1652–1657 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang, F. et al. Kinetics of aquation and anation of ruthenium(ii) arene anticancer complexes, acidity and X-ray structures of aqua adducts. Chem. Eur. J. 9, 5810–5820 (2003).

    CAS  PubMed  Google Scholar 

  36. Bacac, M. et al. The hydrolysis of the anti-cancer ruthenium complex NAMI-A affects its DNA binding and antimetastatic activity: an NMR evaluation. J. Inorg. Chem. 98, 402–412 (2004).

    CAS  Google Scholar 

  37. Chatlas, J., van Eldik, R. & Keppler, B. K. Spontaneous aquation reactions of a promising tumor inhibitor trans-imidazolium-tetrachlorobis(imidazole)ruthenium(iii). trans-HIm[RuCl4(Im)2]. Inorg. Chim. Acta 233, 59–63 (1995).

    CAS  Google Scholar 

  38. Dhubhghaill, O. M. N., Hagen, W. R., Keppler, B. K., Lipponerc, K. & Sadler, P. J. Aquation of the anticancer complex trans-[RuCI4(Him)2] - (Him = imidazole). J. Chem. Soc. Dalton Trans. 0, 3305–3310 (1994).

    Google Scholar 

  39. Debreczeni, J. É. et al. Ruthenium half-sandwich complexes bound to protein kinase Pim-1. Angew. Chem. Int. Ed. 45, 1580–1585 (2006).

    CAS  Google Scholar 

  40. Reedijk, J. New clues for platinum antitumor chemistry: Kinetically controlled metal binding to DNA. Proc. Natl Acad. Sci. USA 100, 3611–3616 (2003).

    CAS  PubMed  Google Scholar 

  41. Yamada, H., Koike, T. & Hurst, J. K. Water exchange rates in the diruthenium μ-oxo ion cis. cis-[(bpy)2Ru(OH2)]2O4+. J. Am. Chem. Soc. 123, 12775–12780 (2001).

    CAS  PubMed  Google Scholar 

  42. Klausner, R. D. et al. Receptor-mediated endocytosis of transferrin in K562 cells. J. Am. Chem. Soc. 258, 4715–4724 (1983).

    CAS  Google Scholar 

  43. Singh, M. Transferrin as a targeting ligand for liposomes and anticancer drugs. Curr. Pharm. Des. 5, 443–451 (1999).

    CAS  PubMed  Google Scholar 

  44. Alessio, E. Thirty years of the drug candidate NAMI-A and the myths in the field of ruthenium anticancer compounds: a personal perspective. Eur. J. Inorg. Chem. 12, 1549–1560 (2017).

    Google Scholar 

  45. Suss-Fink, G. Arene ruthenium complexes as anticancer agents. Dalton Trans. 39, 1673–1688 (2010).

    PubMed  Google Scholar 

  46. Pongratz, M. et al. Transferrin binding and transferrin-mediated cellular uptake of the ruthenium coordination compound KP1019, studied by means of AAS, ESI-MS and CD spectroscopy. J. Anal. At. Spectrom. 19, 46–51 (2004).

    CAS  Google Scholar 

  47. Thota, S., Rodrigues, D. A., Crans, D. C. & Barreiro, E. J. Ru(ii) compounds: next-generation anticancer metallotherapeutics? J. Med. Chem. 61, 5805–5821 (2018).

    CAS  Google Scholar 

  48. Bergamo, A., Messori, L., Piccioli, F., Cochietto, M. & Sava, G. Biological role of adduct formation of the ruthenium(iii) complex NAMI-A with serum albumin and serum transferrin. Invest. New Drugs 21, 401–411 (2003).

    CAS  PubMed  Google Scholar 

  49. Hartinger, C. G. et al. From bench to bedside — preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(iii)] (KP1019 or FFC14A). J. Inorg. Biochem. 100, 891–904 (2006).

    CAS  PubMed  Google Scholar 

  50. Hartinger, G., Jakupec, M. A., Zorbas-Seifried, S. & Groessl, M. KP1019, a new redox-active anticancer agent — preclinical development and results of a clinical phase i study in tumor patients. Chem. Biodivers. 5, 2140–2155 (2008).

    CAS  PubMed  Google Scholar 

  51. Heffeter, P., Atil, B., Kryeziu, K. & Groza, D. The ruthenium compound KP1339 potentiates the anticancer activity of sorafenib in vitro and in vivo. Eur. J. Cancer. 15, 3366–3375 (2013).

    Google Scholar 

  52. Bytzek, A. K., Koellensperger, G., Keppler, B. K. & Hartinger, G. Biodistribution of the novel anticancer drug sodium trans-[tetrachloridobis(1H-indazole)ruthenate(iii)] KP-1339/IT139 in nude BALB/c mice and implications on its mode of action. J. Inorg. Biochem. 160, 250–255 (2016).

    CAS  PubMed  Google Scholar 

  53. Fong, J. et al. A novel class of ruthenium-based photosensitizers effectively kills in vitro cancer cells and in vivo tumors. Photochem. Photobiol. Sci. 14, 2014–2023 (2015).

    CAS  PubMed  Google Scholar 

  54. Larson, N. & Ghandehari, H. Polymeric conjugates for anti-cancer drug delivery. Chem. Mater. 24, 840–853 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Zeng, L. et al. The development of anticancer ruthenium complexes: from single molecule compounds to nanomaterials. Chem. Soc. Rev. 46, 5571–5804 (2017). This article is a complete review with an overview of anticancer Ru(ii) complexes and an introduction for Ru(ii)-based nanomaterials systems.

    Google Scholar 

  56. Ulbrich, K. et al. Targeted drug delivery with polymers and magnetic nanoparticles: covalent and noncovalent approaches, release control, and clinical studies. Chem. Rev. 116, 5338–5431 (2016).

    CAS  PubMed  Google Scholar 

  57. Langer, R. & Tirrell, D. A. Designing materials for biology and medicine. Nature 428, 487–492 (2004).

    CAS  PubMed  Google Scholar 

  58. Lenz, R. W. Biodegradable polymers. Adv. Polym. Sci. 107, 1–40 (1993).

    CAS  Google Scholar 

  59. Albertsson, A. C. & Karlsson, S. in Chemistry and Technology of Biodegradable Polymers (ed. Griffin, G.) 7–17 (Springer Netherlands, 1994).

  60. Li, S. & Vert, M. in Degradable Polymers: Principles and Applications (eds Scott, G. & Gilead, D.) 43–87 (Chapman & Hall, London, 1995).

  61. Kopeček, J. & Ulbrich, K. Biodegradation of biomedical polymers. Prog. Polym. Sci. 9, 1–58 (1983).

    Google Scholar 

  62. Albertsson, A. C. & Varma, I. K. Aliphatic polyesters: synthesis, properties and applications. Adv. Polym. Sci. 157, 1–40 (2002).

    CAS  Google Scholar 

  63. Matlaga, B. F., Yasenchak, L. P. & Salthouse, T. N. Tissue response to implanted polymers: the significance of sample shape. J. Biomed. Mater. Res. 10, 391–397 (1976).

    CAS  PubMed  Google Scholar 

  64. Liechty, W. B., Kryscio, D. R., Slaughter, B. V. & Peppas, N. A. Polymers for drug delivery systems. Annu. Rev. Chem. Biomol. Eng. 1, 149–173 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Esser-Kahn, A. P., Odom, S. A., Sottos, N. R., White, S. R. & Moore, J. S. Triggered release from polymer capsules. Macromolecules 44, 5539–5553 (2011).

    CAS  Google Scholar 

  66. Kamaly, N., Yameen, B., Wu, J. & Farokhzad, O. C. Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem. Rev. 116, 2602–2663 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Wong, P. T. & Choi, S. K. Mechanisms of drug release in nanotherapeutic delivery systems. Chem. Rev. 115, 3388–3432 (2015).

    CAS  PubMed  Google Scholar 

  68. Holohan, C., Schaeybroeck, Van, S., Longley, D. B. & Johnston, P. G. Cancer drug resistance: an evolving paradigm. Nat. Rev. Cancer 13, 714–726 (2013).

    CAS  PubMed  Google Scholar 

  69. Blair, J. M., Webber, M. A., Baylay, A. J., Ogbolu, D. O. & Piddock, L. J. V. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol. 13, 42–51 (2014).

    PubMed  Google Scholar 

  70. Maeda, H., Bharate, G. Y. & Daruwalla, J. Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. Eur. J. Pharm. Biopharm. 71, 409–419 (2009).

    CAS  PubMed  Google Scholar 

  71. Matsumura, Y. & Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agents Smancs. Cancer Res. 46, 6387–6392 (1986).

    CAS  PubMed  Google Scholar 

  72. Maeda, H., Wu, J., Sawa, T., Matsumura, Y. & Hori, K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Release 65, 271–284 (2000).

    CAS  PubMed  Google Scholar 

  73. Maeda, H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv. Enzyme Regul. 41, 189–207 (2001).

    CAS  PubMed  Google Scholar 

  74. Maeda, H., Fang, J., Inutsuka, T. & Kitamoto, Y. Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implication. Int. Immunopharmacol. 3, 319–328 (2003).

    CAS  PubMed  Google Scholar 

  75. Lammers, T., Kiessling, F., Hennink, W. E. & Storm, G. Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J. Control. Release 161, 175–187 (2012).

    CAS  PubMed  Google Scholar 

  76. Prabhakar, U., Blakey, D. C. & Maeda, H. Challenges and key considerations of the enhanced permeability and retention effect (EPR) for nanomedicine drug delivery in oncology. Cancer Res. 15, 2412–2417 (2013).

    Google Scholar 

  77. Cheng, L., Wang, C. & Liu, Z. Functional nanomaterials for phototherapies of cancer. Chem. Rev. 114, 10869–10939 (2014).

    CAS  PubMed  Google Scholar 

  78. Prabhu, R. H., Patravale, V. B. & Joshi, M. D. Polymeric nanoparticles for targeted treatment in oncology: current insights. Int. J. Nanomed. 10, 1001–1018 (2015).

    CAS  Google Scholar 

  79. Portney, N. G. & Ozkan, M. Nano-oncology: drug delivery, imaging, and sensing. Anal. Bioanal. Chem. 384, 620–630 (2006).

    CAS  PubMed  Google Scholar 

  80. Shastri, V. P. Non-degradable biocompatible polymers in medicine: past, present and future. Curr. Pharm. Biotechnol. 4, 331–337 (2003).

    CAS  PubMed  Google Scholar 

  81. Svenson, S. Dendrimers as versatile platform in drug delivery applications. Eur. J. Pharm. Biopharm. 71, 445–462 (2009).

    CAS  PubMed  Google Scholar 

  82. Nair, L. S. & Laurencin, C. T. Biodegradable polymers as biomaterials. Prog. Polym. Sci. 32, 762–798 (2007).

    CAS  Google Scholar 

  83. Hofmann, D., Entrialgo-Castaño, M., Kratz, K. & Lendlein, A. Knowledge-based approach towards hydrolytic degradation of polymer-based biomaterials. Adv. Mater. 21, 3237–3245 (2009).

    CAS  PubMed  Google Scholar 

  84. Allison, S. D. Effect of structural relaxation on the preparation and drug release behavior of poly(lactic-co-glycolic) acid microparticle drug delivery systems. J. Pharm. Sci. 97, 2022–2035 (2008).

    CAS  PubMed  Google Scholar 

  85. Thomas, C. M. & Lutz, J. F. Precision synthesis of biodegradable polymers. Angew. Chem. Int. Ed. 50, 9244–9246 (2011).

    CAS  Google Scholar 

  86. Bader, H., Ringsdorf, H. & Schmidt, B. Water soluble polymers in medicine. Macromol. Mater. Eng. 123, 457–485 (1984).

    Google Scholar 

  87. Kopeček, J. Soluble biomedical polymers. Polym. Med. 7, 191–221 (1977).

    Google Scholar 

  88. Yokoyama, M. Clinical applications of polymeric micelle carrier systems in chemotherapy and image diagnosis of solid tumors. J. Exp. Clin. Med. 3, 151–158 (2011).

    CAS  Google Scholar 

  89. Choi, H. S. et al. Renal clearance of quantum dots. Nat. Biotechnol. 25, 1165–1170 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Douliez, J.-P., Navailles, L. & Nallet, F. Self-assembly of fatty acid-alkylboladiamine salts. Langmuir 22, 622–627 (2006).

    CAS  PubMed  Google Scholar 

  91. Nishiyama, N. & Kataoka, K. Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery. Pharmacol. Ther. 112, 630–648 (2006).

    CAS  PubMed  Google Scholar 

  92. Torchilin, V. P. Structure and design of polymeric surfactant-based drug delivery systems. J. Control. Release 73, 137–172 (2001).

    CAS  PubMed  Google Scholar 

  93. Evans, F. D. & Wennerström, H. The Colloidal Domain: Where Physics, Chemistry, Biology, and Technology Meet 2nd edn (Wiley-Blackwell, 1999).

  94. Nicolas, J., Mura, S., Brambilla, D., Mackiewicz, N. & Couvreur, P. Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chem. Soc. Rev. 42, 1147–1235 (2013).

    CAS  PubMed  Google Scholar 

  95. Mora-huertas, C. E., Fessi, H. & Elaissari, A. Polymer-based nanocapsules for drug delivery. Int. J. Pharm. 385, 113–142 (2010).

    CAS  PubMed  Google Scholar 

  96. Sant, V. P., Smith, D. & Leroux, J. Novel pH-sensitive supramolecular assemblies for oral delivery of poorly water soluble drugs: preparation and characterization. J. Control. Release 97, 301–312 (2004).

    CAS  PubMed  Google Scholar 

  97. Hu, M., Zhu, J. & Qiu, L. Y. Polymer micelle-based combination therapy of paclitaxel and resveratrol with enhanced and selective antitumor activity. RSC Adv. 4, 64151–64161 (2014).

    CAS  Google Scholar 

  98. Tyrrell, Z. L., Shen, Y. & Radosz, M. Fabrication of micellar nanoparticles for drug delivery through the self-assembly of block copolymers. Prog. Polym. Sci. 35, 1128–1143 (2010).

    CAS  Google Scholar 

  99. Newcome, G. R., Moorefield, C. N. & Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Prespectives (VCH-Weinheim, 1996).

  100. Dvornic, P. R. & Tomalia, D. A. Recent advances in dendritic polymers. Curr. Opin. Colloid Interface Sci. 1, 221–235 (1996).

    CAS  Google Scholar 

  101. Letchford, K. & Burt, H. A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur. J. Pharm. Biopharm. 65, 259–269 (2007).

    CAS  PubMed  Google Scholar 

  102. Slomkowski, S. Functionalized biodegradable nano- and microspheres for medical applications. Macromol. Symp. 288, 121–129 (2010).

    CAS  Google Scholar 

  103. Rabea, E. I., Badawy, M. E. T., Stevens, C. V., Smagghe, G. & Steurbaut, W. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules 4, 1457–1465 (2003).

    CAS  PubMed  Google Scholar 

  104. Muxika, A., Etxabide, A., Uranga, J., Guerrero, P. & de la Caba, K. Chitosan as a bioactive polymer: processing, properties and applications. Int. J. Biol. Macromol. 105, 1358–1368 (2017).

    CAS  PubMed  Google Scholar 

  105. Tsvirko, M., Tkaczyk, S., Kozak, M. & Kalota, B. Luminescent temperature sensor based on [Ru(bpy)3]2+ incorporated into chitosan. Funct. Mater. 20, 127–132 (2013).

    CAS  Google Scholar 

  106. Tønnesen, H. H. & Karlsen, J. Alginate in drug delivery systems. Drug Dev. Ind. Pharm. 28, 621–630 (2002).

    PubMed  Google Scholar 

  107. Heathman, T. R. J. et al. The translation of cell-based therapies: clinical landscape and challenges. Regen. Med. 10, 49–64 (2015).

    CAS  PubMed  Google Scholar 

  108. Mount, N. M., Ward, S. J., Kefalas, P. & Hyllner, J. Cell-based therapy technology classifications and translational challenges. Phil. Trans. R. Soc. B 370, 20150017 (2015).

    PubMed  Google Scholar 

  109. Kumar, S., Kumar, R., Ratnam, A., Mishra, N. C. & Ghosh, K. Novel drug delivery system for photoinduced nitric oxide (NO) delivery. Inorg. Chem. Commun. 53, 23–25 (2015).

    CAS  Google Scholar 

  110. Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R. & Rudzinski, W. E. Biodegradable polymeric nanoparticles as drug delivery devices. J. Control. Release 70, 1–20 (2001).

    CAS  PubMed  Google Scholar 

  111. Panyam, J. & Labhasetwar, V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev. 55, 329–347 (2003).

    CAS  PubMed  Google Scholar 

  112. Hans, M. & Lowman, A. Biodegradable nanoparticles for drug delivery and targeting. Curr. Opin. Solid State Mater. Sci. 6, 319–327 (2002).

    CAS  Google Scholar 

  113. Zolnik, B. S. & Burgess, D. J. Effect of acidic pH on PLGA microsphere degradation and release. J. Control. Release 122, 338–344 (2007).

    CAS  PubMed  Google Scholar 

  114. Mishra, B., Patel, B. B. & Tiwari, S. Colloidal nanocarriers: a review on formulation technology, types and applications toward targeted drug delivery. Nanomedicine 6, 9–24 (2010).

    CAS  PubMed  Google Scholar 

  115. Fischer, B. et al. Poly(lactic acid) nanoparticles of the lead anticancer ruthenium compound KP1019 and its surfactant-mediated activation. Dalton Trans. 43, 1096–1104 (2014).

    CAS  PubMed  Google Scholar 

  116. Kerwin, B. A., Kerwin, B. A. & Kerwin, B. A. Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways. J. Pharm. Sci. 97, 2924–2935 (2008).

    CAS  PubMed  Google Scholar 

  117. Boeuf, G. et al. Encapsulated ruthenium(ii) complexes in biocompatible poly(D, L-lactide-co-glycolide) nanoparticles for application in photodynamic therapy. Chempluschem 79, 171–180 (2014).

    CAS  Google Scholar 

  118. Gomes, A. J., Barbougli, P. A., Espreafico, E. M. & Tfouni, E. Trans-[Ru(NO)(NH3)4(py)](BF4)3∙H2O encapsulated in PLGA microparticles for delivery of nitric oxide to B16-F10 cells: cytotoxicity and phototoxicity. J. Inorg. Biochem. 102, 757–766 (2008).

    CAS  PubMed  Google Scholar 

  119. Gomes, A. J., Espreafico, E. M. & Tfouni, E. Trans-[Ru(NO)Cl(cyclam)](PF6)2 and [Ru(NO)(Hedta)] incorporated in PLGA nanoparticles for the delivery of nitric oxide to B16-F10 cells: cytotoxicity and phototoxicity. Mol. Pharm. 10, 3544–3554 (2013).

    CAS  PubMed  Google Scholar 

  120. de Souza Oliveira, F. et al. Development of biodegradable nanoparticles containing trans-RuCl([15]ane)(NO)]2+ as nitric oxide donor. Trends Inorg. Chem. 10, 27–34 (2008).

    Google Scholar 

  121. Bohlender, C., Landfester, K., Crespy, D. & Schiller, A. Unconventional non-aqueous emulsions for the encapsulation of a phototriggerable NO-donor complex in polymer nanoparticles. Part. Part. Syst. Charact. 30, 138–142 (2013).

    CAS  Google Scholar 

  122. Bohlender, C. et al. Light-triggered NO release from a nanofibrous non-woven. J. Mater. Chem. 22, 8785–8792 (2012).

    CAS  Google Scholar 

  123. Moreno, M. J. et al. Production of singlet oxygen by Ru(dpp(SO3)2)3 incorporated in polyacrylamide PEBBLES. Sens Actuators B Chem. 90, 82–89 (2003).

    CAS  Google Scholar 

  124. Yin, H., Fang, J., Liao, L., Nakamura, H. & Maeda, H. Styrene-maleic acid copolymer-encapsulated CORM2, a water-soluble carbon monoxide (CO) donor with a constant CO-releasing property, exhibits therapeutic potential for inflammatory bowel disease. J. Control. Release 187, 14–21 (2014).

    CAS  PubMed  Google Scholar 

  125. Dickerson, M., Howerton, B., Bae, Y. & Glazer, E. Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer. J. Mater. Chem. B. 4, 394–408 (2016).

    CAS  PubMed  Google Scholar 

  126. Appold, M. et al. Multi-stimuli responsive block copolymers as a smart release platform for a polypyridyl ruthenium complex. Polym. Chem. 8, 890–900 (2017).

    CAS  Google Scholar 

  127. Shachaf, Y., Gonen-Wadmany, M. & Seliktar, D. The biocompatibility of Pluronic®F127 fibrinogen-based hydrogels. Biomaterials 31, 2836–2847 (2010).

    CAS  PubMed  Google Scholar 

  128. Batrakova, E. V. & Kabanov, A. V. Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J. Control. Release 130, 98–106 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Riess, G. Micellization of block copolymers. Prog. Polym. Sci. 28, 1107–1170 (2003).

    CAS  Google Scholar 

  130. Khan, A. A., Fullerton-Shirey, S. K. & Howard, S. S. Easily prepared ruthenium-complex nanomicelle probes for two-photon quantitative imaging of oxygen in aqueous media. RSC Adv. 5, 291–300 (2015).

    CAS  Google Scholar 

  131. Papkovsky, D. B. & Dmitriev, R. I. Biological detection by optical oxygen sensing. Chem. Soc. Rev. 42, 8700 (2013).

    CAS  PubMed  Google Scholar 

  132. Barry, N. P. E. et al. Precious metal carborane polymer nanoparticles: characterisation of micellar formulations and anticancer activity. Faraday Discuss. 175, 229–240 (2014).

    CAS  PubMed  Google Scholar 

  133. Gregoriadis, G. The carrier potential of liposomes in biology and medecine. N. Engl. J. Med. 295, 765–770 (1976).

    CAS  PubMed  Google Scholar 

  134. Gao, W., Hu, C.-M., Ronnie, J., Fang, H. & Zhang, L. Liposome-like nanostructures for drug delivery. J. Mater. Chem. B 1, 6569–6585 (2013).

    CAS  Google Scholar 

  135. Kasera, N. K., Sharma, P. K. & Gupta, R. Recent advancement and patents of the lipid polymer hybrid nanoparticles. Peertechz J. Med. Chem. Res. 2, 25–29 (2016).

    Google Scholar 

  136. Maranho, D. S., De Lima, R. G., Primo, F. L., Da Silva, R. S. & Tedesco, A. C. Photoinduced nitric oxide and singlet oxygen release from ZnPC liposome vehicle associated with the nitrosyl ruthenium complex: synergistic effects in photodynamic therapy application. Photochem. Photobiol. 85, 705–713 (2009).

    CAS  PubMed  Google Scholar 

  137. de Lima, R. G., Tedesco, A. C., da Silva, R. S. & Lawrence, M. J. Ultradeformable liposome loaded with zinc phthalocyanine and [Ru(NH.NHq)(tpy)NO]3+ for photodynamic therapy by topical application. Photodiagnosis Photodyn. Ther. 19, 184–193 (2017).

    PubMed  Google Scholar 

  138. Lim, W. H. & Lawrence, M. J. Influence of surfactant and lipid chain length on the solubilisation of phosphatidylcholine vesicles by micelles comprised of polyoxyethylene sorbitan monoesters. Colloids Surf. A Physicochem. Eng. Asp. 250, 449–457 (2004).

    CAS  Google Scholar 

  139. Simeone, L. et al. Nucleolipid nanovectors as molecular carriers for potential applications in drug delivery. Mol. Biosyst. 7, 3075–3086 (2011).

    CAS  PubMed  Google Scholar 

  140. Mangiapia, G. et al. Ruthenium-based complex nanocarriers for cancer therapy. Biomaterials 33, 3770–3782 (2012).

    CAS  PubMed  Google Scholar 

  141. Mangiapia, G. et al. Anticancer cationic ruthenium nanovectors: from rational molecular design to cellular uptake and bioactivity. Biomacromolecules 14, 2549–2560 (2013).

    CAS  PubMed  Google Scholar 

  142. Montesarchio, D. et al. A new design for nucleolipid-based Ru(iii) complexes as anticancer agents. Dalton Trans. 42, 16697–16708 (2013). This study uses a polymer–lipid hybrid as a nanovehicle for the delivery of a Ru complex. The decoration of the surface of the ‘liposome’ is achieved by self-assembly and incorporation of an amphiphilic Ru complex in the lipid membrane.

    CAS  PubMed  Google Scholar 

  143. Askes, S. H. C., Meijer, M. S., Bouwens, T., Landman, I. & Bonnet, S. Red light activation of Ru(ii) polypyridyl prodrugs via triplet–triplet annihilation upconversion: feasibility in air and through meat. Molecules 21, E1460 (2016).

    PubMed  Google Scholar 

  144. Ringsdorf, H. Structure and properties of pharmacologically active polymers. J. Polym. Sci. Polym. Symp. 51, 135–153 (2007).

    Google Scholar 

  145. Fuertges, F. & Abuchowski, A. The clinical efficacy of poly(ethylene glycol)-modified proteins. J. Control. Release 11, 139–148 (1990).

    CAS  Google Scholar 

  146. Duncan, R., Lloyd, J. B. & Kopec˘ek, J. Degradation of side chains of N-(2 hydroxypropyl) methacrylamide copolymers by lysosomal enzymes. Biochem. Biophys. Res. Commun. 94, 284–290 (1980).

    CAS  PubMed  Google Scholar 

  147. Duncan, R. Soluble synthetic polymers as potential drug carriers. Adv. Polym. Sci. 57, 53–100 (1984).

    Google Scholar 

  148. Hasegawa, U., Van Der Vlies, A. J., Simeoni, E., Wandrey, C. & Hubbell, J. A. Carbon monoxide-releasing micelles for immunotherapy. J. Am. Chem. Soc. 132, 18273–18280 (2010). The study presents the first example of CO delivery using a Ru-based metallopolymer.

    CAS  PubMed  Google Scholar 

  149. Nguyen, D., Nguyen, T. K., Rice, S. A. & Boyer, C. CO-releasing polymers exert antimicrobial activity. Biomacromolecules 16, 2776–2786 (2015).

    CAS  PubMed  Google Scholar 

  150. Nguyen, D., Adnan, N. N. M., Oliver, S. & Boyer, C. The Interaction of CORM-2 with block copolymers containing poly(4-vinylpyridine): macromolecular scaffolds for carbon monoxide delivery in biological systems. Macromol. Rapid Commun. 37, 739–744 (2016).

    CAS  PubMed  Google Scholar 

  151. Halpenny, G. M., Olmstead, M. M. & Mascharak, P. K. Incorporation of a designed ruthenium nitrosyl in PolyHEMA hydrogel and light-activated delivery of NO to myoglobin. Inorg. Chem. 46, 6601–6606 (2007).

    CAS  PubMed  Google Scholar 

  152. Xu, L. Q. Ruthenium(ii)-terpyridine complexes-containing glyconanoparticles for one- and two-photon excited fluorescence imaging. Eur. Polym. J. 71, 279–288 (2015).

    CAS  Google Scholar 

  153. Wang, Y. et al. Nanoparticles of chitosan conjugated to organo-ruthenium complexes. Inorg. Chem. Front. 3, 1058–1064 (2016).

    CAS  Google Scholar 

  154. Vadivel, T. & Dhamodaran, M. Synthesis, characterization and antibacterial studies of ruthenium(iii) complexes derived from chitosan schiff base. Int. J. Biol. Macromol. 90, 44–52 (2016).

    CAS  PubMed  Google Scholar 

  155. Sharma, R. et al. Ruthenium tris(2-pyridylmethyl)amine as an effective photocaging group for nitriles. Inorg. Chem. 53, 3272–3274 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Li, A., Turro, C. & Kodanko, J. J. Ru(ii) polypyridyl complexes as photocages for bioactive compounds containing nitriles and aromatic heterocycles. Chem. Commun. 54, 1280–1290 (2018).

    CAS  Google Scholar 

  157. Sun, W. et al. An amphiphilic ruthenium polymetallodrug for combined photodynamic therapy and photochemotherapy in vivo. Adv. Mater. 29, 1603702 (2017).

    Google Scholar 

  158. Sun, W. et al. Ruthenium-containing block copolymer assemblies: red-light-responsive metallopolymers with tunable nanostructures for enhanced cellular uptake and anticancer phototherapy. Adv. Healthc. Mater. 5, 467–473 (2016).

    CAS  PubMed  Google Scholar 

  159. Rapp, T. L., Highley, C. B., Manor, B. C., Burdick, J. A. & Dmochowski, I. J. Ruthenium-crosslinked hydrogels with rapid, visible-light degradation. Chem. Eur. J. 24, 2328–2333 (2018).

    CAS  PubMed  Google Scholar 

  160. Corbin, P. S., Webb, M. P., McAlvin, J. E. & Fraser, C. L. Biocompatible polyester macroligands: New subunits for the assembly of star-shaped polymers with luminescent and cleavable metal cores. Biomacromolecules 2, 223–232 (2001).

    CAS  PubMed  Google Scholar 

  161. Nawaby, A. V., Farah, A. A., Liao, X., Pietro, W. J. & Day, M. Biodegradable open cell foams of telechelic poly(ε-caprolactone) macroligand with ruthenium(ii) chromophoric subunits via sub-critical CO2 processing. Biomacromolecules 6, 2458–2461 (2005).

    CAS  PubMed  Google Scholar 

  162. Valente, A. et al. First polymer ‘ruthenium-cyclopentadienyl’ complex as potential anticancer agent. J. Inorg. Biochem. 127, 79–81 (2013).

    CAS  PubMed  Google Scholar 

  163. Johnson, R. M. & Fraser, C. L. Metalloinitiation routes to biocompatible poly(lactic acid) and poly(acrylic acid) stars with luminescent ruthenium tris(bipyridine) cores. Biomacromolecules 5, 580–588 (2004). This study uses a Ru(ii) complex as a metalloinitiator for the ring-opening polymerization of esters.

    CAS  PubMed  Google Scholar 

  164. Neu, M., Fischer, D. & Kissel, T. Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. J. Gene Med. 7, 992–1009 (2005).

    CAS  PubMed  Google Scholar 

  165. Kircheis, R., Wightman, L. & Wagner, E. Design and gene delivery activity of modified polyethylenimines. Adv. Drug Deliv. Rev. 53, 341–358 (2001).

    CAS  PubMed  Google Scholar 

  166. Fiore, G. L. et al. Ruthenium(ii) tris(bipyridine)-centered poly(ethylenimine) for gene delivery. Biomacromolecules 8, 2829–2835 (2007).

    CAS  PubMed  Google Scholar 

  167. Mitchell-Koch, J. T., Reed, T. M. & Borovik, A. S. Light-activated transfer of nitric oxide from a porous material. Angew. Chem. Int. Ed. 43, 2806–2809 (2004). The study provides the first example of NO photorelease from a polymer-encapsulated Ru complex.

    CAS  Google Scholar 

  168. Libera, M. et al. Amphiphilic dendritic copolymers of tert-butyl-glycidylether and glycidol as a nanocontainer for an anticancer ruthenium complex. J. Polym. Sci. A Polym. Chem. 52, 3488–3497 (2014).

    CAS  Google Scholar 

  169. Govender, P. et al. Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds. J. Organomet. Chem. 694, 3470–3476 (2009). This study presents an example of multi-Ru dendrimers and the relationship between the size and the toxicity of metallodendrimers.

    CAS  Google Scholar 

  170. Govender, P. et al. Antiproliferative activity of chelating N,O and N,N-ruthenium(ii)arene functionalised poly(propyleneimine) dendrimer scaffolds. Dalton Trans. 40, 1158–1167 (2011).

    CAS  PubMed  Google Scholar 

  171. Govender, P. et al. First- and second-generation heterometallic dendrimers containing ferrocenyl−ruthenium(ii)−arene motifs: synthesis, structure, electrochemistry, and preliminary cell proliferation studies. Organometallics 33, 5535–5545 (2014).

    CAS  Google Scholar 

  172. Govender, P. et al. The influence of RAPTA moieties on the antiproliferative activity of peripheral-functionalised poly(salicylaldiminato) metallodendrimers. Dalton Trans. 4, 1267–1277 (2013).

    Google Scholar 

  173. Ruggi, A. et al. Dendritic ruthenium(ii)-based dyes tuneable for diagnostic or therapeutic applications. Chem. Eur. J. 17, 464–467 (2011).

    CAS  PubMed  Google Scholar 

  174. Benini, P. G. Z., McGarvey, B. R. & Franco, D. W. Functionalization of PAMAM dendrimers with [Ruiii(edta)(H2O)]. Nitric Oxide 19, 245–251 (2008).

    CAS  PubMed  Google Scholar 

  175. Duncan, R. & Izzo, L. Dendrimer biocompatibility and toxicity. Adv. Drug Deliv. Rev. 57, 2215–2237 (2005).

    CAS  PubMed  Google Scholar 

  176. Armspach, D., Cattalini, M., Constable, E. C., Housecroft, C. E. & Phillips, D. Boron-rich metallodendrimers — mix-and-match assembly of multifunctional metallosupramolecules. Chem. Commun. 1823–1824 (1996).

  177. Housecroft, C. E. Icosahedral building blocks: towards dendrimers with twelve primary branches? Angew. Chem. Int. Ed. 38, 2717–2719 (1999).

    CAS  Google Scholar 

  178. Callari, M., Aldrich-Wright, J. R., De Souza, P. L. & Stenzel, M. H. Polymers with platinum drugs and other macromolecular metal complexes for cancer treatment. Prog. Polym. Sci. 39, 1614–1643 (2014).

    CAS  Google Scholar 

  179. Oberoi, H. S., Nukolova, N. V., Kabanov, A. V. & Bronicha, T. K. Nanocarriers for delivery of platinum anticancer drugs. Adv. Drug Deliv. Rev. 65, 1667–1685 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Geng, Y. et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nat. Nanotechnol. 2, 249–255 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  181. Yang, Y., He, Q., Duan, L., Cui, Y. & Li, J. Assembled alginate/chitosan nanotubes for biological application. Biomaterials 28, 3083–3090 (2007).

    CAS  PubMed  Google Scholar 

  182. Shi, Y. et al. Recent progress and development on polymeric nanomaterials for photothermal therapy: a brief overview. J. Mater. Chem. B 5, 194–206 (2017).

    CAS  Google Scholar 

  183. Komor, A. C. & Barton, J. K. The path for metal complexes to a DNA target. Chem. Commun. 49, 3617–3630 (2013).

    CAS  Google Scholar 

  184. Deweese, J. E. & Osheroff, N. The DNA cleavage reaction of topoisomerase II: wolf in sheep’s clothing. Nucleic Acids Res. 37, 738–748 (2009).

    CAS  PubMed  Google Scholar 

  185. Gopal, Y. N. V., Jayaraju, D. & Kondapi, A. K. Inhibition of topoisomerase II catalytic activity by two ruthenium compounds: a ligand-dependent mode of action. Biochemistry 38, 4382–4388 (1999).

    CAS  PubMed  Google Scholar 

  186. Heffeter, P., Bo, K., Ute, B. & Bernhard, J. Intracellular protein binding patterns of the anticancer ruthenium drugs KP1019 and KP1339. J. Biol. Inorg. Chem. 15, 737–748 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Heffeter, P. et al. Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(iii)] (FFC14A). J. Pharm. Exp. Ther. 312, 281–289 (2005).

    CAS  Google Scholar 

  188. Pa˘unescu, E. et al. Organometallic glutathione S-transferase inhibitors. Organometallics 36, 3313–3321 (2017).

    Google Scholar 

  189. Feng, L. et al. Structurally sophisticated octahedral metal complexes as highly selective protein kinase inhibitors. J. Am. Chem. Soc. 133, 5976–5986 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. Duncan, R., Dimitrijevic, S. & Evagorou, E. The role of polymer conjugates in the diagnosis and treatment of cancer. Pharm. Sci. 6, 237–263 (1996).

    Google Scholar 

  191. Farokhzad, O. C. & Langer, R. Impact of nanotechnology on drug delivery. ACS Nano 3, 16–20 (2009).

    CAS  PubMed  Google Scholar 

  192. Li, S. & Huang, L. Pharmacokinetics and biodistribution of nanoparticles. Mol. Pharm. 5, 496–504 (2008).

    CAS  PubMed  Google Scholar 

  193. Noguchi, Y., Wu, J., Duncan, R., Ulbrich, K. & Akaike, T. Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues. Jpn J. Cancer Res. 89, 307–314 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  194. Chauhan, V. P. et al. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat. Nanotechnol. 7, 383–388 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Longmire, M., Choyke, P. L. & Kobayashi, H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine 3, 703–717 (2012).

    Google Scholar 

  196. Nag, O. K. & Awasthi, V. Surface engineering of liposomes for stealth behavior. Pharmaceutics 5, 542–569 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Immordino, M. L., Dosio, F. & Cattel, L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int. J. Nanomed. 1, 297–315 (2006).

    CAS  Google Scholar 

  198. Stolnik, S., Illum, L. & Davis, S. S. Long circulating microparticulate drug carriers. Adv. Drug Deliv. Rev. 16, 195–214 (1995).

    CAS  Google Scholar 

  199. Allen, T. M., Hansen, C. & Rutledge, J. Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. Biochim. Biophys. Acta 981, 27–35 (1989).

    CAS  PubMed  Google Scholar 

  200. Garay, R. P., El-Gewely, R., Armstrong, J. K., Garratty, G. & Richette, P. Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents. Expert Opin. Drug Deliv. 9, 1319–1323 (2012).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge funding from École Nationale Supérieure de Chimie de Paris (ENSCP), the Centre National de la Recherche Scientifique (CNRS), a European Research Council (ERC) Consolidator Grant PhotoMedMet GA 681679 (G.G.), the Swiss National Science Foundation Grant Sinergia CRSII5_173718 (G.G.) and the Investissements d’Avenir programme launched by the French government and implemented by the Agence Nationale de la Recherche (ANR), reference ANR-10-IDEX-0001-02 PSL (G.G.). C.M.T. thanks the Institut Universitaire de France (IUF) for financial support.

Author information

Authors and Affiliations

Authors

Contributions

E.V, C.M.T. and G.G. are the major contributors to this Review, with Y.C.O. contributing to a lesser extent.

Corresponding authors

Correspondence to Christophe M. Thomas or Gilles Gasser.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Villemin, E., Ong, Y.C., Thomas, C.M. et al. Polymer encapsulation of ruthenium complexes for biological and medicinal applications. Nat Rev Chem 3, 261–282 (2019). https://doi.org/10.1038/s41570-019-0088-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41570-019-0088-0

This article is cited by

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research