Abstract
Two major obstacles facing cancer nanomedicine are the tendency of nanoparticles to be taken up by normal tissues and organs and the nanoparticles' inability to efficiently penetrate solid tumours. Although substantial efforts have been made to improve the intratumoural delivery of nanotherapeutics, many strategies have failed to produce meaningful clinical benefits. Recent advances in the field of immuno-oncology have led to drugs that boost the host's own immune system to fight cancer. In contrast to conventional therapies, which often target cancer cells, immunotherapies stimulate immune cells in ways that promote their recognition and the eradication of tumours. In this Perspective, we posit that this approach represents a new framework for cancer nanomedicine, and that immune-targeted nanomedicines could generate tumouricidal effects without the need to overcome the pathophysiological barriers that are intrinsic to the tumour microenvironment and that hinder nanoparticle delivery. The rational design of new immuno-oncology nanomedicines provides opportunities for developing the next generation of nanotherapeutics for cancer patients.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$99.00 per year
only $8.25 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Allen, T. M. & Cullis, P. R. Drug delivery systems: entering the mainstream. Science 303, 1818–1822 (2004).
Hurria, A. et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J. Clin. Oncol. 29, 3457–3465 (2011).
Sawyer, C. Targeted cancer therapy. Nature 432, 294–297 (2004).
Haber, D. A., Gray, N. S. & Baselga, J. The evolving war on cancer. Cell 145, 19–24 (2011).
O'Brien, S. G. et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 348, 994–1004 (2003).
Engelman, J. A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550–562 (2009).
Peer, D. et al. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotech. 2, 751–760 (2007).
Chow, E. K. & Ho, D. Cancer nanomedicine: from drug delivery to imaging. Sci. Transl. Med. 5, 216rv4 (2013).
Harris, J. M. & Chess, R. B. Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2, 214–221 (2003).
Roderiguez, P. L. et al. Minimal “self” peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science 339, 971–975 (2013).
Parodi, A. et al. Synthetic nanoparticles functionalized with biomimetic leukocyte membrane possess cell-like functions. Nat. Nanotech. 8, 61–68 (2013).
Hu, C. J. et al. Nanoparticle biointerfacing by platelet membrane cloaking. Nature 526, 118–121 (2015).
Cho, K., Wang, X., Nie, S., Chen, Z. & Shin, D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 4, 1310–1316 (2008).
Farokhzad, O. C. et al. Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc. Natl Acad. Sci. USA 103, 6315–6320 (2006).
Wang, A. Z., Langer, R. & Farokhzad, O. C. Nanoparticle delivery of cancer drugs. Annu. Rev. Med. 63, 185–198 (2012).
Trédan, O., Galmarini, C. M., Patel, K. & Tannock, I. F. Drug resistance and the solid tumor microenvironment. J. Natl Cancer Inst. 99, 1441–1454 (2007).
Jain, R. K. & Stylianopoulos, T. Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 7, 653–664 (2010).
Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407, 249–257 (2000).
Hashizume, H. et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am. J. Pathol. 156, 1363–1380 (2000).
Matsumura, Y. & Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387–6392 (1986).
Prabhakar, U. et al. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 73, 2412–2417 (2013).
Blanco, E., Shen, H. & Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951 (2015).
Sykes, E. A. et al. Tailoring nanoparticle designs to target cancer based on tumor pathophysiology. Proc. Natl Acad. Sci. USA 113, E1142–E1151 (2016).
Perrault, S. D., Walkey, C., Jennings, T., Fischer, H. C. & Chan, W. C. W. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett. 9, 1909–1915 (2009).
Jiang, W., Kim, B. Y. S., Rutka, J. T. & Chan, W. C. W. Advances and challenges of nanotechnology-based drug delivery systems. Expert Opin. Drug Deliv. 4, 621–633 (2007).
von Roemeling, C. A., Jiang, W., Chan, C. K., Weissman, I. L. & Kim, B. Y. S. Breaking down the barriers to precision cancer nanomedicine. Trends Biotechnol. 35, 159–171 (2017).
Wong, C. et al. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc. Natl Acad. Sci. USA 108, 2426–2431 (2010).
Wilhelm, S. et al. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 1, 16014 (2016).
Tsoi, K. M. et al. Mechanism of hard-nanomaterial clearance by the liver. Nat. Mater. 15, 1212–1221 (2016).
De Jong, W. H. et al. Particle size-dependent organ distribution of gold nanoparticles after intravenous administration. Biomaterials 29, 1912–1919 (2008).
Xiao, K. et al. The effect of surface charge on in vivo distribution of PEG-oligocholic acid based micellar nanoparticles. Biomaterials 32, 3435–3446 (2011).
Tenzer, S. et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat. Nanotech. 8, 772–781 (2013).
Cedervall, T. et al. Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl Acad. Sci. USA 104, 2050–2055 (2007).
Walkey, C. D., Olsen, J. B., Guo, H., Emili, A. & Chan, W. C. W. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 134, 2139–2147 (2012).
Walkey, C. D. et al. Protein corona fingerprinting predicts the cellular interactions of gold and silver nanoparticles. ACS Nano 8, 2439–2455 (2014).
Nel, A. E. et al. Understanding biophysicochemical interactions at the nano–bio interface. Nat. Mater. 8 543–557 (2009).
Qie, Y. et al. Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes. Sci. Rep. 6, 26269 (2016).
Wang, H., Wu, L. & Reinhard, B. M. Scavenger receptor mediated endocytosis of silver nanoparticles into J774A.1 macrophages is heterogeneous. ACS Nano 6, 7122–7132 (2012).
Hamilton, A. et al. EORTC 10968: a phase I clinical and pharmacokinetic study of polyethylene glycol liposomal doxorubicin (Caelyx, Doxil) at a 6-week interval in patients with metastatic breast cancer. European Organisation for Research and Treatment of Cancer. Ann. Oncol. 13, 910–918 (2002).
Schottler, S. et al. Protein adsorption is required for stealth effect of poly(ethyleneglycol)- and poly(phosphoester)-coated nanocarriers. Nat. Nanotech. 11, 372–377 (2016).
Hu, C. M. et al. Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl Acad. Sci. USA 108, 10980–10985 (2011).
Guo, Y. et al. Erythrocyte membrane-enveloped polymeric nanoparticles as nanovaccine for induction of antitumor immunity against melanoma. ACS Nano 9, 6918–6933 (2015).
Molinaro, R. et al. Biomimetic proteolipid vesicles for targeting inflamed tissues. Nat. Mater. 15, 1037–1046 (2016).
Felfoul, O. et al. Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nat. Nanotech. 11 941–947 (2016).
Takizawa, H. & Manz, M. G. Macrophage tolerance: CD47–SIRP-α-mediated signals matter. Nat. Immunol. 8, 1287–1289 (2007).
Kurts, C., Panzer, U., Anders, H. J. & Rees, A. J. The immune system and kidney disease: basic concepts and clinical implications. Nat. Rev. Immunol. 13, 738–753 (2013).
Deen, W. M., Lazzara, M. J. & Meyers, B. D. Structural determinants of glomerular permeability. Am. J. Physiol. Renal Physiol. 281, F579–F596 (2001).
Choi, H. S. et al. Renal clearance of quantum dots. Nat. Biotechnol. 25, 1165–1170 (2007).
Liu, J. Y. et al. Renal clearable inorganic nanoparticles: a new frontier of bionanotechnology. Mater. Today 16, 477–486 (December, 2013).
Schrier, R. W. Cancer therapy and renal injury. J. Clin. Invest. 110, 743–745 (2002).
Groothuis, D. R. The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro. Oncol. 2, 45–59 (2000).
Su, L., Mruk, D. D. & Cheng, C. Y. Drug transporters, the blood-testis barrier, and spermatogenesis. J. Endocrinol. 208, 207–223 (2011).
Koffie, R. M. et al. Nanoparticles enhance brain delivery of blood-brain barrier-impermeable probes for in vivo optical and magnetic resonance imaging. Proc. Natl Acad. Sci. USA 108, 18837–18842 (2011).
Zensi, A. et al. Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain. J. Drug Target. 18, 842–848 (2010).
Schroeder, A. et al. Treating metastatic cancer with nanotechnology. Nat. Rev. Cancer 12, 39–50 (2012).
Carpentier, A. et al. Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Sci. Transl. Med. 8, 343re2 (2016).
Maeda, H., Nakamura, H. & Fang, J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. Adv. Drug Deliv. Rev. 65, 71–79 (2013).
Hobbs, S. K. et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc. Natl Acad. Sci. USA 95, 4607–4612 (1998).
Chauhan, V. P. & Jain, R. K. Strategies for advancing cancer nanomedicine. Nat. Mater. 12, 958–962 (2013).
Padera, T. P. et al. Pathology: cancer cells compress intratumour vessels. Nature 427, 695 (2004).
Adiseshaiah, P. P., Crist, R. M., Hook, S. S. & McNeil, S. E. Nanomedicine strategies to overcome the pathophysiological barriers of pancreatic cancer. Nat. Rev. Clin. Oncol. 13, 750–765 (2016).
Balkwill, F. R., Capasso, M. & Hagemann, T. The tumor microenvironment at a glance. J. Cell Sci. 125, 5591–5596 (2012).
Allen, T. M. Ligand-targeted therapeutics in anticancer therapy. Nat. Rev. Cancer 2, 750–763 (2002).
Kim, B. Y. S. et al. Biodegradable quantum dot nanocomposites enable live cell labeling and imaging of cytoplasmic targets. Nano Lett. 8, 3887–3892 (2008).
Gao, X., Cui, Y., Levenson, R. M., Chung, L. W. K. & Nie, S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22, 969–976 (2004).
Choi, H. S. et al. Design considerations for tumour-targeted nanoparticles. Nat. Nanotech. 5 42–47 (2010).
Peng, L. et al. Combinatorial chemistry identifies high-affinity peptidomimetics against α4β1 integrin for in vivo tumor imaging. Nat. Chem. Biol. 2, 381–389 (2006).
Jiang, W., Kim, B. Y. S., Rutka, J. T. & Chan, W. C. W. Nanoparticle-mediated cellular response is size-dependent. Nat. Nanotech. 3, 145–150 (2008).
Scott, A. M., Wolchok, J. D. & Old, L. J. Antibody therapy of cancer. Nat. Rev. Cancer 12, 278–287 (2012).
Chan, A. C. & Carter, P. J. Therapeutic antibodies for autoimmunity and inflammation. Nat. Rev. Immunol. 10, 301–316 (2010).
Van Cutsem, E. et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N. Engl. J. Med. 360, 1408–1417 (2009).
Hudis, C. A. Trastuzumab-mechanism of action and use in clinical practice. N. Engl. J. Med. 357, 39–51 (2007).
Cheson, B. D. & Leonard, J. P. Monoclonal antibody therapy for B-cell non-Hodgkin's lymphoma. N. Engl. J. Med. 359, 613–626 (2008).
Verma, S. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367, 1783–1791 (2012).
Tolcher, A. W. et al. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J. Clin. Oncol. 17, 478–484 (1999).
Kim, B. Y. S., Rutka, J. T. & Chan, W. C. W. Nanomedicine. N. Engl. J. Med. 363, 2434–2443 (2010).
Joyce, J. A. Therapeutic targeting of the tumor microenvironment. Cancer Cell 7, 513–520 (2005).
Arap, W., Pasqualini, R. & Ruoslahti, E. Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279, 377–380 (1998).
Sugahara, K. N. et al. Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell 16, 510–520 (2009).
Ruoslahti, E., Bhatia, S. N. & Sailor, M. J. Targeting of drugs and nanoparticles to tumors. J. Cell. Biol. 188, 759–768 (2010).
81 Teesalu, T., Sugahara, K. N., Kotamraju, V. R. & Ruoslahti, E. C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration. Proc. Natl Acad. Sci. USA 106, 16157–16162 (2009).
Simberg, D. et al. Biomimetic amplification of nanoparticle homing to tumors. Proc. Natl Acad. Sci. USA 104, 932–936 (2007).
Messerschmidt, S. K. et al. Targeted lipid-coated nanoparticles: delivery of tumor necrosis factor-functionalized particles to tumor cells. J. Control. Release 137, 69–77 (2009).
Weissleder, R., Nahrendorf, M. & Pittet, M. J. Imaging macrophages with nanoparticles. Nat. Mater. 13, 125–138 (2014).
Zhang, B. et al. Targeting fibronectins of glioma extracellular matrix by CLT1 peptide-conjugated nanoparticles. Biomaterials 35, 4088–4098 (2014).
Carmeliet, P. & Jain, R. K. Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat. Rev. Drug. Discov. 10, 417–427 (2011).
Chauhan, V. P. et al. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat. Nanotech. 7, 383–388 (2012).
Jiang, W., Huang, Y. H., An, Y. & Kim, B. Y. S. Remodeling tumor vasculature to enhance delivery of intermediate-sized nanoparticles. ACS Nano 9, 8689–8696 (2015).
Cabral, H. et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotech. 6, 815–823 (2011).
Pardoll, D. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12, 252–264 (2012).
Garon, E. B. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 372, 2018–2028 (2015).
Motzer, R. J. et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med. 373, 1803–1813 (2015).
Larkin, J. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23–34 (2015).
Nghiem, P. T. et al. PD-1 blockade with pembrolizumab in advanced Merkel cell carcinoma. N. Engl. J. Med. 374, 2542–2552 (2016).
Yang, Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J. Clin. Invest. 125, 3335–3337 (2015).
Palucka, K. & Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer 12, 265–277 (2012).
Ravichandran, K. S. Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity 35, 445–455 (2011).
Chao, M. P. et al. Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci. Transl. Med. 2, 63ra94 (2010).
Fadok, V. A. et al. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405, 85–90 (2000).
Morvan, M. G. & Lanier, L. L. NK cells and cancer: you can teach innate cells new tricks. Nat. Rev. Cancer 16, 7–19 (2016).
Jaiswal, S. et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 138, 271–285 (2009).
Willingham, S. B. et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc. Natl Acad. Sci. USA 109, 6662–6667 (2012).
Tsai, R. K. & Discher, D. E. Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells. J. Cell Biol. 180, 989–1003 (2008).
Sharma, P. & Allison, J. P. The future of immune checkpoint therapy. Science 348, 56–61 (2015).
Anderson, A. C. Tim-3, a negative regulator of anti-tumor immunity. Curr. Opin . Immunol. 24, 213–216 (2012).
Bubeník, J. MHC class I down-regulation: tumour escape from immune surveillance?. Int. J. Oncol. 25, 487–491 (2004).
Marvel, D. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J. Clin. Invest. 125, 3356–3364 (2015).
Holmgaard, R. B. et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell Rep. 13, 412–424 (2015).
Eil, R. et al. Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature 537, 539–543 (2016).
Biswas, S. K. & Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889–896 (2010).
Kerkar, S. P. & Restifo, N. P. Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 72, 3125–3130 (2012).
Kranz, L. M. et al. Systemic RNA delivery to dendritic cells exploits antiviral defense for cancer immunotherapy. Nature 534, 396–401 (2016).
Sager, H. B. et al. RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. Sci. Transl. Med. 8, 342ra80> (2016).
Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5, 161–171 (2005).
Hawkin, M. J., Soon-Shiong, P. & Desai, N. Protein nanoparticles as drug carriers in clinical medicine. Adv. Drug Deliv. Rev. 60, 876–885 (2008).
Postow, M. A. et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 372, 2006–2017 (2015).
Le, D. T. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372, 2509–2520 (2015).
Ansell, S. M. et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 372, 311–319 (2015).
Li, A. V. et al. Generation of effector memory T cell-based mucosal and systemic immunity with pulmonary nanoparticle vaccination. Sci. Transl. Med. 5, 204ra130 (2013).
Cho, N. H. et al. A multifunctional core–shell nanoparticle for dendritic cell-based cancer immunotherapy. Nat. Nanotech. 6, 675–682 (2011).
Moon, J. J. et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat. Mater. 10, 243–251 (2011).
Lizotte, P. H. et al. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nat. Nanotech. 11 295–303 (2016).
Li, H., Li, Y., Jiao, J. & Hu, H. M. Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response. Nat. Nanotech. 6, 645–650 (2011).
Albert, L. J. & Inman, R. D. Molecular mimicry and autoimmunity. N. Engl. J. Med. 341, 2068–2074 (1999).
Leuschner, F. et al. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat. Biotechnol. 29, 1005–1010 (2011).
Yin, H. et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat. Biotechnol. 34, 328–333 (2016).
Sunshine, J. C. & Green, J. J. Nanoengineering approaches to the design of artificial antigen-presenting cells. Nanomedicine 8, 1173–1189 (2013).
Andre, F., Escudier, B., Angevin, E., Tursz, T. & Zitvogel, L. Exosomes for cancer immunotherapy. Ann. Oncol. 15, iv141–iv144 (2004).
Théry, C., Ostrowski, M. & Segura, E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 9, 581–593 (2009).
Utsugi-Kobukai, S., Fujimaki, H., Hotta, C., Nakazawa, M. & Minami, M. MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells. Immunol. Lett. 89, 125–131 (2003).
Pitt, J. M. et al. Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. J. Immunol. 193, 1006–1011 (2014).
Besse, B. et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology 5, e1071008 (2016).
133 Chen, Q. et al. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 7, 13193 (2016).
Kullberg, M., Martinson, H., Mann, K. & Anchordoquy, T. J. Complement C3 mediated targeting of liposomes to granulocytic myeloid derived suppressor cells. Nanomedicine 11, 1355–1363 (2015).
Novobrantseva, T. I. et al. Systemic RNAi-mediated gene silencing in nonhuman primate and rodent myeloid cells. Molecular Therapy Nucleic Acids 1, e4 (2012).
Zanganeh, S. et al. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat. Nanotech. 11, 986–994 (2016).
Vétizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).
Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).
Rizvi, N. A. et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128 (2015).
Chen, P. L. et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov. 6, 1–11 (2016).
Herbst, R. S. et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387, 1540–1550 (2016).
Gainor, J. F. Moving programmed death-1 inhibitors to the front lines in non-small-cell lung cancer. J. Clin. Oncol. 34, 2953–2955 (2016).
Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012).
St John, A. L. et al. Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes. Nat. Mater. 11, 250–257 (2012).
Goldberg, M. S. Immunoengineering: how nanotechnology can enhance cancer immunotherapy. Cell 161, 201–204 (2015).
Sato, K. et al. Spatially selective depletion of tumor-associated regulatory T cells with near-infrared photoimmunotherapy. Sci. Transl. Med. 8, 352ra110 (2016).
Weissig, V., Pettinger, T. K. & Murdock, N. Nanopharmaceuticals (part 1): products on the market. Int. J. Nanomedicine 9, 4357–4373 (2014).
Bozzuto, G. & Molinari, A. Liposomes as nanomedical devices. Int. J. Nanomedicine 10, 975–999 (2015).
Arvedson, T., O'Kelly, J. & Yang, B. B. Design rationale and development approach for pegfilgrastim as a long-acting granulocyte colony-stimulating factor. BioDrugs 29, 185–198 (2015).
Duncan, R. Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer 6, 688–701 (2006).
Aaron, C. & Anselmo, S. M. Nanoparticles in the clinic. Bioeng. Transl. Med. 1, 10–29 (2016).
Park, J. et al. Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat. Mater. 1, 1 895–905 (2012).
Eck, W. et al. Anti-CD4-targeted gold nanoparticles induce specific contrast enhancement of peripheral lymph nodes in X-ray computed tomography of live mice. Nano Lett. 10, 2318–2322 (2010).
Acknowledgements
This work was supported by The Jorge and Leslie Bacardi Fund for the study of Regenerative Medicine (to B.Y.S.K.), the Mayo Clinic Center for Regenerative Medicine (to B.Y.S.K.), the James C. and Sara K. Kennedy Award (to B.Y.S.K.), the Mayo Clinic Center for Individualized Medicine Gerstner Family Award (to B.Y.S.K.), the JLG Brain Cancer Foundation and Richard D. and Darlene R. DeMars Award (to B.Y.S.K.), the Strawn Family Development Award (to B.Y.S.K.), the Helene Houle Career Development Award in Neurologic Surgery Research (to B.Y.S.K.) and the National Cancer Institute's Cancer Center Support (Core) Grant CA016672 (to The University of Texas MD Anderson Cancer Center). The authors thank C. Wogan of the MD Anderson Cancer Center's Division of Radiation Oncology for editorial assistance.
Author information
Authors and Affiliations
Contributions
W.J., J.C. and B.Y.S.K. conceived the work. W.J., C.A.V. and Y.C. carried out the literature search. W.J. and Y.Q. designed and generated the figures. All authors contributed to writing the manuscript.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Jiang, W., von Roemeling, C., Chen, Y. et al. Designing nanomedicine for immuno-oncology. Nat Biomed Eng 1, 0029 (2017). https://doi.org/10.1038/s41551-017-0029
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41551-017-0029
This article is cited by
-
Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics
Nature Nanotechnology (2024)
-
Engineering siRNA therapeutics: challenges and strategies
Journal of Nanobiotechnology (2023)
-
Engineering nanomaterial physical characteristics for cancer immunotherapy
Nature Reviews Bioengineering (2023)
-
Nanocarriers for cancer nano-immunotherapy
Drug Delivery and Translational Research (2023)
-
A nano-innate immune system activator for cancer therapy in a 4T1 tumor-bearing mouse model
Journal of Nanobiotechnology (2022)