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WIREs Nanomed Nanobiotechnol
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Nanotechnology platforms for cancer immunotherapy

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Abstract Various cancer therapies have advanced remarkably over the past decade. Unlike the direct therapeutic targeting of tumor cells, cancer immunotherapy is a new strategy that boosts the host's immune system to detect specific cancer cells for efficient elimination. Nanoparticles incorporating immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance antitumor immunity. Such nanoparticle‐based cancer immunotherapies have received considerable attention and have been extensively studied in recent years. This review thus focuses on nanoparticle‐based platforms (especially naturally derived nanoparticles and synthetic nanoparticles) utilized in recent advances; summarizes delivery systems that incorporate various immune‐modulating agents, including peptides and nucleic acids, immune checkpoint inhibitors, and other small immunostimulating agents; and introduces combinational cancer immunotherapy with nanoparticles, especially nanoparticle‐based photo‐immunotherapy and nanoparticle‐based chemo‐immunotherapy. Undoubtedly, the recent studies introduced in this review prove that nanoparticle‐incorporated cancer immunotherapy is a highly promising treatment modality for patients with cancer. Nonetheless further research is needed to solve safety concerns and improve efficacy of nanoplatform‐based cancer immunotherapy for future clinical application. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Immune actions in the cycle of cancer immunotherapy
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(a) Coadministration of in situ vaccination (PXV) and chemotherapy (DOX) potentiate the antitumor effect. (Reprinted with permission from K. L. Lee et al. () Copyright © 2017, American Chemical Society). (b) TLNP delivery system encapsulating PTX and TLR4 agonist led to significant tumor regression. (Reprinted with permission from (Roy, Singh, Upadhyay, & Bhaskar, ) Copyright © 2013 Elsevier B.V.). (c) Combinatory delivery of TLR7/8 agonist and DOX for a synergetic antitumor effect. (Reprinted with permission from Y. Liu et al. () © 2017 Acta Materialia Inc. Published by Elsevier Ltd.)
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RPTDH/R848 nanoparticles for breast tumor inhibition through enhanced permeability and retention (EPR). (Reprinted with permission from P. Zhou et al. () © 2019 Elsevier B.V)
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(a) Self‐assembled m‐HA nanoparticle encapsulating 1‐MT and aPD1 with a synergistic microneedle (MN)‐based transcutaneous delivery system. (Reprinted with permission from Ye et al. () © American Association of Pharmaceutical Scientists 2016). (b) Lipoprotein‐mimicking nanodiscs system loading doxorubicin (DOX) combined with IgG for combinatory antitumor therapy. (Reprinted with permission from Kuai et al. () © American Association for the Advancement of Science 2018). (c) ZnP nanoparticles encapsulating a photosensitizer pyrolipid could sensitize tumors to increase tumor immunogenicity by combinational immunotherapy. (Reprinted with permission from Duan et al. () © Copyright © 2016, American Chemical Society). (d) siCTLA‐4‐encapsulated nanoparticles (NPsiCTLA‐4) could enhance T cell‐mediated immune responses by blocking CTLA‐4 and suppressing overall growth of tumors. (Reprinted with permission from S. Y. Li et al. () © 2016 Elsevier B.V)
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(a) pH‐responsive diblock copolymers (DEAEMA‐co‐BMA) with linear, core‐cross‐linked, or hyperbranched structures. (b) A pyridyl disulfide functionalized monomer (PDSMA) was used for antigen conjugation. The ability of copolymers to enhance MHC‐I antigen presentation by dendritic cells was evaluated in three types of structure. (Reprinted with permission from Wilson et al. () © American Association of Pharmaceutical Scientists 2014)
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(a) Structures of cationic Amphiphiles 1 and 2 with mannose‐mimicking shikimoyl‐ and quinoyl‐groups the in head‐group region; Structure 3 was their mannosyl analogue. (Reprinted with permission from Srinivas et al. (). Copyright © 2012 Elsevier Ltd.). (b) Tumor size in a subcutaneous tumor model with the control of Poly I:C/CpG‐ODN incorporated into cationic lipid‐based nanoparticles. (Reprinted with permission from C. Liu, Chu, et al. (). Copyright © 2018 Elsevier B.V.). (c) (i) Particle size and polydispersity index of RNA‐LPX constituted with DOTMA/DOPE liposomes. (ii) Bioluminescence imaging of BALB/c mice after in vivo injection of Luc‐LPX. Pie charts showed relative contribution of each organ to total signal. (Reprinted with permission from Kranz et al. (). Copyright © 2016, Springer Nature)
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Nanoparticles‐based platforms that incorporate immune‐modulating agents for cancer immunotherapy
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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