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WIREs Nanomed Nanobiotechnol

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Nanomedicine approaches to improve cancer immunotherapy

Advanced Review

Hui Qiu, Yuanzeng Min, Zach Rodgers, Longzhen Zhang, Andrew Z. Wang

Published Online: Mar 10 2017

DOI: 10.1002/wnan.1456

Full article on Wiley Online Library: HTML PDF

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Significant advances have been made in the field of cancer immunotherapy by orchestrating the body's immune system to eradicate cancer cells. However, safety and efficacy concerns stemming from the systemic delivery of immunomodulatory compounds limits cancer immunotherapies expansion and application. In this context, nanotechnology presents a number of advantages, such as targeted delivery to immune cells, enhanced clinical outcomes, and reduced adverse events, which may aid in the delivery of cancer vaccines and immunomodulatory agents. With this in mind, a diverse range of nanomaterials with different physicochemical characteristics have been developed to stimulate the immune system and battle cancer. In this review, we will focus on some recent developments and the potential advantages of utilizing nanotechnology within the field of cancer immunotherapy. WIREs Nanomed Nanobiotechnol 2017, 9:e1456. doi: 10.1002/wnan.1456 This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Cancer immunity cycle. The progression of cancer recognition and immunity typically cycles through the release of TAAs, presentation of TAAs by APCs, priming of T cells by activated APCs, migration of T cells back to the tumor, killing of tumor cells by T cells, and release of more TAAs. Nanoparticle approaches to cancer immunotherapy should focus on improving the progression of these steps via delivery of antigen and immune modulators that increase response and reduce immunosuppressive mechanisms. APC, antigen‐presenting cell; TAA, tumor‐associated antigen.

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Nanoparticles for cancer immunotherapy. Nanoparticles with different structures can be used cancer immunotherapy, which includes (a) dendrimer, (b) micelles, (c) virus‐like nanoparticles, (d) liposomes, (e) gold nanoparticles, and so on.

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Cancer immunosuppression mechanisms. Antitumor immunity can be suppressed by recruited immune cells that secrete immunosuppressive compounds within the TME. Tumor cells themselves can also suppress immunity by expressing surface molecules that cause T cell anergy and exhaustion. APM, antigen processing machine; CTL, cytotoxic T lymphocyte; CTLA‐4, CTL‐associated protein‐4; DC, dendritic cell; NP, nanoparticle; IDO, indoleamine 2,3‐dioxygenase; MDSC, myeloid‐derived suppressive cell; NK, natural killer; TCR, T cell receptor; TGF‐β, transforming growth factor beta; TAM, tumor‐associated macrophages. (Reprinted with permission from Ref . Copyright 2015 Elsevier)

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The sizes of vaccine delivery systems and pathogenic agents. APC, antigen‐presenting cell; ISCOM, immunostimulatory complex; VLP, virus‐like particle. (Reprinted with permission from Ref . Copyright 2010 Nature Publishing Group)

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Cancer cell membrane‐coated nanoparticles for cancer vaccination. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society)

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Strategies of nanoimmunotherapy for cancer. NPs can deliver antigens and adjuvants to induce DC maturation. NP formulation can enhance the presentation of TAAs. Additionally, NPs can restore T cell antitumor function by delivering CTLA‐4 or PD‐1/PD‐L1 antibodies (anti‐CTLA‐4 or anti‐PD‐1/ PD‐L1) that stop anergy. CTL, cytotoxic T lymphocyte; CTLA‐4, CTL‐associated protein‐4; DC, dendritic cell; NP, nanoparticle; PD‐1, programmed death‐1.

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References

Chen, DS, Mellman, I. Oncology meets immunology: the cancer‐immunity cycle. Immunity 2013, 39:1–10.
Shao, K, Singha, S, Clemente‐Casares, X, Tsai, S, Yang, Y, Santamaria, P. Nanoparticle‐based immunotherapy for cancer. ACS Nano 2015, 9:16–30.
Anguille, S, Smits, EL, Lion, E, van Tendeloo, VF, Berneman, ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol 2014, 15:e257–e267.
Liu, H, Irvine, DJ. Guiding principles in the design of molecular bioconjugates for vaccine applications. Bioconjug Chem 2015, 26:791–801.
Palucka, K, Banchereau, J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer 2012, 12:265–277.
Sehgal, K, Ragheb, R, Fahmy, TM, Dhodapkar, MV, Dhodapkar, KM. Nanoparticle‐mediated combinatorial targeting of multiple human dendritic cell (DC) subsets leads to enhanced T cell activation via IL‐15‐dependent DC crosstalk. J Immunol 2014, 193:2297–2305.
Cruz, LJ, Tacken, PJ, Rueda, F, Domingo, JC, Albericio, F, Figdor, CG. Targeting nanoparticles to dendritic cells for immunotherapy. Methods Enzymol 2012, 509:143–163.
Sehgal, K, Dhodapkar, KM, Dhodapkar, MV. Targeting human dendritic cells in situ to improve vaccines. Immunol Lett 2014, 162:59–67.
Fang, RH, Kroll, AV, Zhang, L. Nanoparticle‐based manipulation of antigen‐presenting cells for cancer immunotherapy. Small 2015, 11:5483–5496.
Gao, P, Xia, G, Bao, Z, Feng, C, Cheng, X, Kong, M, Liu, Y, Chen, X. Chitosan based nanoparticles as protein carriers for efficient oral antigen delivery. Int J Biol Macromol 2016, 91:716–723.
Maji, M, Mazumder, S, Bhattacharya, S, Choudhury, ST, Sabur, A, Shadab, M, Bhattacharya, P, Ali, N. A lipid based antigen delivery system efficiently facilitates MHC class‐I antigen presentation in dendritic cells to stimulate CD8(+) T cells. Sci Rep 2016, 6:27206.
Rietscher, R, Schroder, M, Janke, J, Czaplewska, J, Gottschaldt, M, Scherliess, R, Hanefeld, A, Schubert, US, Schneider, M, Knolle, PA, et al. Antigen delivery via hydrophilic PEG‐b‐PAGE‐b‐PLGA nanoparticles boosts vaccination induced T cell immunity. Eur J Pharm Biopharm 2016, 102:20–31.
Gavin, AL, Hoebe, K, Duong, B, Ota, T, Martin, C, Beutler, B, Nemazee, D. Adjuvant‐enhanced antibody responses in the absence of toll‐like receptor signaling. Science 2006, 314:1936–1938.
Shapira, L, Soskolne, WA, Houri, Y, Barak, V, Halabi, A, Stabholz, A. Protection against endotoxic shock and lipopolysaccharide‐induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion. Infect Immun 1996, 64:825–828.
Gupta, RK, Siber, GR. Adjuvants for human vaccines—current status, problems and future prospects. Vaccine 1995, 13:1263–1276.
Cho, K, Wang, X, Nie, S, Chen, ZG, Shin, DM. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 2008, 14:1310–1316.
Gutjahr, A, Phelip, C, Coolen, AL, Monge, C, Boisgard, AS, Paul, S, Verrier, B. Biodegradable polymeric nanoparticles‐based vaccine adjuvants for lymph nodes targeting. Vaccines (Basel) 2016, 4:E34.
Krieg, AM. Therapeutic potential of Toll‐like receptor 9 activation. Nat Rev Drug Discov 2006, 5:471–484.
Bourquin, C, Anz, D, Zwiorek, K, Lanz, AL, Fuchs, S, Weigel, S, Wurzenberger, C, von der Borch, P, Golic, M, Moder, S, et al. Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity. J Immunol 2008, 181:2990–2998.
Sokolova, V, Knuschke, T, Kovtun, A, Buer, J, Epple, M, Westendorf, AM. The use of calcium phosphate nanoparticles encapsulating Toll‐like receptor ligands and the antigen hemagglutinin to induce dendritic cell maturation and T cell activation. Biomaterials 2010, 31:5627–5633.
Schlosser, E, Mueller, M, Fischer, S, Basta, S, Busch, DH, Gander, B, Groettrup, M. TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses. Vaccine 2008, 26:1626–1637.
Hamdy, S, Molavi, O, Ma, Z, Haddadi, A, Alshamsan, A, Gobti, Z, Elhasi, S, Samuel, J, Lavasanifar, A. Co‐delivery of cancer‐associated antigen and Toll‐like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell‐mediated anti‐tumor immunity. Vaccine 2008, 26:5046–5057.
Li, H, Li, Y, Jiao, J, Hu, HM. Alpha‐alumina nanoparticles induce efficient autophagy‐dependent cross‐presentation and potent antitumour response. Nat Nanotechnol 2011, 6:645–650.
Fang, RH, Hu, CM, Luk, BT, Gao, W, Copp, JA, Tai, Y, O`Connor, DE, Zhang, L. Cancer cell membrane‐coated nanoparticles for anticancer vaccination and drug delivery. Nano Lett 2014, 14:2181–2188.
Klippstein, R, Pozo, D. Nanotechnology‐based manipulation of dendritic cells for enhanced immunotherapy strategies. Nanomed Nanotechnol Biol Med 2010, 6:523–529.
Kempf, M, Mandal, B, Jilek, S, Thiele, L, Voros, J, Textor, M, Merkle, HP, Walter, E. Improved stimulation of human dendritic cells by receptor engagement with surface‐modified microparticles. J Drug Target 2003, 11:11–18.
Dhodapkar, MV, Sznol, M, Zhao, B, Wang, D, Carvajal, RD, Keohan, ML, Chuang, E, Sanborn, RE, Lutzky, J, Powderly, J, et al. Induction of antigen‐specific immunity with a vaccine targeting NY‐ESO‐1 to the dendritic cell receptor DEC‐205. Sci Transl Med 2014, 6:232ra51.
Kokate, RA, Chaudhary, P, Sun, X, Thamake, SI, Maji, S, Chib, R, Vishwanatha, JK, Jones, HP. Rationalizing the use of functionalized poly‐lactic‐co‐glycolic acid nanoparticles for dendritic cell‐based targeted anticancer therapy. Nanomedicine (Lond) 2016, 11:479–494.
Qian, Y, Jin, H, Qiao, S, Dai, Y, Huang, C, Lu, L, Luo, Q, Zhang, Z. Targeting dendritic cells in lymph node with an antigen peptide‐based nanovaccine for cancer immunotherapy. Biomaterials 2016, 98:171–183.
Mansourian, M, Badiee, A, Jalali, SA, Shariat, S, Yazdani, M, Amin, M, Jaafari, MR. Effective induction of anti‐tumor immunity using p5 HER‐2/neu derived peptide encapsulated in fusogenic DOTAP cationic liposomes co‐administrated with CpG‐ODN. Immunol Lett 2014, 162:87–93.
Bachmann, MF, Jennings, GT. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 2010, 10:787–796.
Estrella, V, Chen, T, Lloyd, M, Wojtkowiak, J, Cornnell, HH, Ibrahim‐Hashim, A, Bailey, K, Balagurunathan, Y, Rothberg, JM, Sloane, BF, et al. Acidity generated by the tumor microenvironment drives local invasion. Cancer Res 2013, 73:1524–1535.
Kapadia, CH, Perry, JL, Tian, S, Luft, JC, DeSimone, JM. Nanoparticulate immunotherapy for cancer. J Control Release 2015, 219:167–180.
Dunn, GP, Old, LJ, Schreiber, RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004, 21:137–148.
Park, J, Wrzesinski, SH, Stern, E, Look, M, Criscione, J, Ragheb, R, Jay, SM, Demento, SL, Agawu, A, Licona Limon, P, et al. Combination delivery of TGF‐beta inhibitor and IL‐2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat Mater 2012, 11:895–905.
Sacchetti, C, Rapini, N, Magrini, A, Cirelli, E, Bellucci, S, Mattei, M, Rosato, N, Bottini, N, Bottini, M. In vivo targeting of intratumor regulatory T cells using PEG‐modified single‐walled carbon nanotubes. Bioconjug Chem 2013, 24:852–858.
Zhu, S, Niu, M, O`Mary, H, Cui, Z. Targeting of tumor‐associated macrophages made possible by PEG‐sheddable, mannose‐modified nanoparticles. Mol Pharm 2013, 10:3525–3530.
Zhao, Y, Huo, M, Xu, Z, Wang, Y, Huang, L. Nanoparticle delivery of CDDO‐Me remodels the tumor microenvironment and enhances vaccine therapy for melanoma. Biomaterials 2015, 68:54–66.
Lu, Y, Miao, L, Wang, Y, Xu, Z, Zhao, Y, Shen, Y, Xiang, G, Huang, L. Curcumin micelles remodel tumor microenvironment and enhance vaccine activity in an advanced melanoma model. Mol Ther 2016, 24:364–374.
Wang, C, Xu, L, Liang, C, Xiang, J, Peng, R, Liu, Z. Immunological responses triggered by photothermal therapy with carbon nanotubes in combination with anti‐CTLA‐4 therapy to inhibit cancer metastasis. Adv Mater 2014, 26:8154–8162.
Nakamura, Y, Mochida, A, Choyke, PL, Kobayashi, H. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem 2016, 27:2225–2238.
Fang, J, Nakamura, H, Maeda, H. The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 2011, 63:136–151.
Wilhelm, S, Tavares, AJ, Dai, Q, Ohta, S, Audet, J, Dvorak, HF, Chan, WCW. Analysis of nanoparticle delivery to tumours. Nat Rev Mater 2016, 1:16014.
Elhissi, AM, Ahmed, W, Hassan, IU, Dhanak, VR, D`Emanuele, A. Carbon nanotubes in cancer therapy and drug delivery. J Drug Deliv 2012, 2012:837327.
Kim, A, Miura, Y, Ishii, T, Mutaf, OF, Nishiyama, N, Cabral, H, Kataoka, K. Intracellular delivery of charge‐converted monoclonal antibodies by combinatorial design of block/homo polyion complex micelles. Biomacromolecules 2016, 17:446–453.
Chen, M, Ouyang, H, Zhou, S, Li, J, Ye, Y. PLGA‐nanoparticle mediated delivery of anti‐OX40 monoclonal antibody enhances anti‐tumor cytotoxic T cell responses. Cell Immunol 2014, 287:91–99.
Twyman‐Saint Victor, C, Rech, AJ, Maity, A, Rengan, R, Pauken, KE, Stelekati, E, Benci, JL, Xu, B, Dada, H, Odorizzi, PM, et al. Radiation and dual checkpoint blockade activate non‐redundant immune mechanisms in cancer. Nature 2015, 520:373–377.
Lei, C, Liu, P, Chen, B, Mao, Y, Engelmann, H, Shin, Y, Jaffar, J, Hellstrom, I, Liu, J, Hellstrom, KE. Local release of highly loaded antibodies from functionalized nanoporous support for cancer immunotherapy. J Am Chem Soc 2010, 132:6906–6907.
Kwong, B, Gai, SA, Elkhader, J, Wittrup, KD, Irvine, DJ. Localized immunotherapy via liposome‐anchored anti‐CD137 + IL‐2 prevents lethal toxicity and elicits local and systemic antitumor immunity. Cancer Res 2013, 73:1547–1558.
Li, Y, Fang, M, Zhang, J, Wang, J, Song, Y, Shi, J, Li, W, Wu, G, Ren, J, Wang, Z, et al. Hydrogel dual delivered celecoxib and anti‐PD‐1 synergistically improve antitumor immunity. Oncoimmunology 2016, 5:e1074374.
Kosmides, AKSJ. Dual‐targeting nanoparticles for reprogrammed T cell responses in the tumor microenvironment. J Immunother Cancer 2014, 2:P108.
Li, SY, Liu, Y, Xu, CF, Shen, S, Sun, R, Du, XJ, Xia, JX, Zhu, YH, Wang, J. Restoring anti‐tumor functions of T cells via nanoparticle‐mediated immune checkpoint modulation. J Control Release 2016, 231:17–28.
Teo, PY, Yang, C, Whilding, LM, Parente‐Pereira, AC, Maher, J, George, AJ, Hedrick, JL, Yang, YY, Ghaem‐Maghami, S. Ovarian cancer immunotherapy using PD‐L1 siRNA targeted delivery from folic acid‐functionalized polyethylenimine: strategies to enhance T cell killing. Adv Healthc Mater 2015, 4:1180–1189.
Roeven, MW, Hobo, W, van der Voort, R, Fredrix, H, Norde, WJ, Teijgeler, K, Ruiters, MH, Schaap, N, Dolstra, H. Efficient nontoxic delivery of PD‐L1 and PD‐L2 siRNA into dendritic cell vaccines using the cationic lipid SAINT‐18. J Immunother 2015, 38:145–154.
Xu, Z, Wang, Y, Zhang, L, Huang, L. Nanoparticle‐delivered transforming growth factor‐beta siRNA enhances vaccination against advanced melanoma by modifying tumor microenvironment. ACS Nano 2014, 8:3636–3645.
Christian, DA, Hunter, CA. Particle‐mediated delivery of cytokines for immunotherapy. Immunotherapy 2012, 4:425–441.
Kedar, E, Braun, E, Rutkowski, Y, Emanuel, N, Barenholz, Y. Delivery of cytokines by liposomes. II. Interleukin‐2 encapsulated in long‐circulating sterically stabilized liposomes: immunomodulatory and anti‐tumor activity in mice. J Immunother Emphasis Tumor Immunol 1994, 16:115–124.
ten Hagen, TL, Seynhaeve, AL, van Tiel, ST, Ruiter, DJ, Eggermont, AM. Pegylated liposomal tumor necrosis factor‐alpha results in reduced toxicity and synergistic antitumor activity after systemic administration in combination with liposomal doxorubicin (Doxil) in soft tissue sarcoma‐bearing rats. Int J Cancer 2002, 97:115–120.
Neelapu, SS, Gause, BL, Harvey, L, Lee, ST, Frye, AR, Horton, J, Robb, RJ, Popescu, MC, Kwak, LW. A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma. Blood 2007, 109:5160–5163.
Anderson, PM, Hanson, DC, Hasz, DE, Halet, MR, Blazar, BR, Ochoa, AC. Cytokines in liposomes: preliminary studies with IL‐1, IL‐2, IL‐6, GM‐CSF and interferon‐gamma. Cytokine 1994, 6:92–101.
Buonaguro, L, Tagliamonte, M, Tornesello, ML, Buonaguro, FM. Developments in virus‐like particle‐based vaccines for infectious diseases and cancer. Expert Rev Vaccines 2011, 10:1569–1583.
Smith, DM, Simon, JK, Baker, JR. Applications of nanotechnology for immunology. Nat Rev Immunol 2013, 13:592–605.
Ungaro, F, Conte, C, Quaglia, F, Tornesello, ML, Buonaguro, FM, Buonaguro, L. VLPs and particle strategies for cancer vaccines. Expert Rev Vaccines 2013, 12:1173–1193.
Paliard, X, Liu, Y, Wagner, R, Wolf, H, Baenziger, J, Walker, CM. Priming of strong, broad, and long‐lived HIV type 1 p55gag‐specific CD8+ cytotoxic T cells after administration of a virus‐like particle vaccine in rhesus macaques. AIDS Res Hum Retroviruses 2000, 16:273–282.
Zhang, PF, Chen, YX, Zeng, Y, Shen, CG, Li, R, Guo, ZD, Li, SW, Zheng, QB, Chu, CC, Wang, ZT, et al. Virus‐mimetic nanovesicles as a versatile antigen‐delivery system. Proc Natl Acad Sci USA 2015, 112:E6129–E6138.
Lizotte, PH, Wen, AM, Sheen, MR, Fields, J, Rojanasopondist, P, Steinmetz, NF, Fiering, S. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nat Nanotechnol 2016, 11:295–303.
Li, J, Sun, Y, Jia, T, Zhang, R, Zhang, K, Wang, L. Messenger RNA vaccine based on recombinant MS2 virus‐like particles against prostate cancer. Int J Cancer 2014, 134:1683–1694.
Bal, SM, Hortensius, S, Ding, Z, Jiskoot, W, Bouwstra, JA. Co‐encapsulation of antigen and Toll‐like receptor ligand in cationic liposomes affects the quality of the immune response in mice after intradermal vaccination. Vaccine 2011, 29:1045–1052.
Zhou, S, Kawakami, S, Yamashita, F, Hashida, M. Intranasal administration of CpG DNA lipoplex prevents pulmonary metastasis in mice. Cancer Lett 2010, 287:75–81.
Zaks, K, Jordan, M, Guth, A, Sellins, K, Kedl, R, Izzo, A, Bosio, C, Dow, S. Efficient immunization and cross‐priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J Immunol 2006, 176:7335–7345.
Daftarian, P, Kaifer, AE, Li, W, Blomberg, BB, Frasca, D, Roth, F, Chowdhury, R, Berg, EA, Fishman, JB, Al Sayegh, HA, et al. Peptide‐conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen‐presenting cells. Cancer Res 2011, 71:7452–7462.
Bala, I, Hariharan, S, Kumar, MN. PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Ther Drug Carrier Syst 2004, 21:387–422.
Heo, MB, Lim, YT. Programmed nanoparticles for combined immunomodulation, antigen presentation and tracking of immunotherapeutic cells. Biomaterials 2014, 35:590–600.
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 2007, 65:259–269.
Croy, SR, Kwon, GS. Polymeric micelles for drug delivery. Curr Pharm Des 2006, 12:4669–4684.
Luo, Z, Wang, C, Yi, H, Li, P, Pan, H, Liu, L, Cai, L, Ma, Y. Nanovaccine loaded with poly I:C and STAT3 siRNA robustly elicits anti‐tumor immune responses through modulating tumor‐associated dendritic cells in vivo. Biomaterials 2015, 38:50–60.
Jeanbart, L, Kourtis, IC, van der Vlies, AJ, Swartz, MA, Hubbell, JA. 6‐Thioguanine‐loaded polymeric micelles deplete myeloid‐derived suppressor cells and enhance the efficacy of T cell immunotherapy in tumor‐bearing mice. Cancer Immunol Immunother 2015, 64:1033–1046.
Min, Y, Caster, JM, Eblan, MJ, Wang, AZ. Clinical translation of nanomedicine. Chem Rev 2015, 115:11147–11190.
Yang, X, Yang, M, Pang, B, Vara, M, Xia, Y. Gold nanomaterials at work in biomedicine. Chem Rev 2015, 115:10410–10488.
Ahn, S, Lee, IH, Kang, S, Kim, D, Choi, M, Saw, PE, Shin, EC, Jon, S. Gold nanoparticles displaying tumor‐associated self‐antigens as a potential vaccine for cancer immunotherapy. Adv Healthc Mater 2014, 3:1194–1199.
Lee, IH, Kwon, HK, An, S, Kim, D, Kim, S, Yu, MK, Lee, JH, Lee, TS, Im, SH, Jon, S. Imageable antigen‐presenting gold nanoparticle vaccines for effective cancer immunotherapy in vivo. Angew Chem Int Ed Engl 2012, 51:8800–8805.
Almeida, JP, Lin, AY, Figueroa, ER, Foster, AE, Drezek, RA. In vivo gold nanoparticle delivery of peptide vaccine induces anti‐tumor immune response in prophylactic and therapeutic tumor models. Small 2015, 11:1453–1459.
Ma, X, Hui, H, Jin, Y, Dong, D, Liang, X, Yang, X, Tan, K, Dai, Z, Cheng, Z, Tian, J. Enhanced immunotherapy of SM5‐1 in hepatocellular carcinoma by conjugating with gold nanoparticles and its in vivo bioluminescence tomographic evaluation. Biomaterials 2016, 87:46–56.

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