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WIREs Nanomed Nanobiotechnol
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Advances of functional nanomaterials for cancer immunotherapeutic applications

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Abstract Immunotherapy has made great progress by modulating the body's own immune system to fight against cancer cells. However, the low response rates of related drugs limit the development of immunotherapy strategies. Fortunately, the advantages of nanotechnology can just make up for this shortcoming. Nanocarriers of diverse systems are utilized to co‐deliver antigens and adjuvants, combined with drugs for immunomodulatory, such as chemotherapy, radiotherapy, and photodynamic. Here we review recent studies on immunotherapy with biomimetic, organic, and inorganic nanomaterials. They are going to potentially overcome the drawbacks in cancer immunotherapy with delivering immunomodulatory drugs, delivering cancer vaccine, and monitoring the immune systems. This article is characterized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Depiction of the complex pathway involved in cancer immunotherapy. Nanoparticle delivery vehicles can play a role at multiple points along this pathway. (Reprinted with permission from Hartshorn et al. (). Copyright 2017 American Chemical Society)
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Macrophage cell tracking positron‐emission tomography (PET) imaging using mesoporous silica nanoparticles via in vivo bio‐orthogonal 18F labeling. (a) Schematic procedure for preparation of aza‐dibenzocyclooctyne (DBCO)‐ligated mesoporous silica NPs (MSNs) (DBCO‐MSNs). (b) Schematic procedure for the in situ synthesis of 18F‐DBCOT‐MSNs into RAW 264.7 macrophage cells in a living specimen by a bio‐orthogonal 18F‐labeling reaction for the cell tracking PET imaging. (c,d) Macrophage cell tracking PET imaging via bioorthogonal 18F‐labeling in tumor model. (a,b) Three‐dimensional reconstruction (upper) and transverse section (lower) combined PET‐CT images of 18F‐labeled azide in U87 MG tumor‐bearing mice treated with only normal RAW 264.7 cells 3 days earlier (control study; c) or in mice treated with DBCO‐MSNs‐RAW cells 1, 3, 6, or 8 days earlier (cell tracking study; d), recorded 1 hr after injection of 18F‐labeled azide. (Reprinted with permission from Jeong et al. (). Copyright 2019 Elsevier)
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Self‐adjuvant PC7A nanoparticles (NPs) for vaccination and tumor immunotherapy. (a) Schematic depiction of the minimalist design of the PC7A nanovaccine. (b) Schematic depiction of the carboxy fluorescein succinimidyl ester method to screen for polymer structures that generate a strong OVA‐specific cytotoxic T lymphocyte (CTL) response. OVA was used as a model antigen and loaded into different polymer NPs. (c) Quantitative comparison of OVA‐specific CTL responses in different NP groups, identifying the PC7A NP as the best candidate. (Reprinted with permission from Luo et al. () Copyright 2017 Springer Nature)
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Antigen‐capturing NPs (AC‐NPs) improve the abscopal effect and cancer immunotherapy by capturing antigens in vivo and in vitro. (a) Schematic depiction of utilizing AC‐NPs to improve cancer immunotherapy. After radiotherapy, AC‐NPs bind to tumor antigens and improve their presentation to DCs. The improved antigen presentation and immune activation is synergistic with αPD‐1 treatment. (b,c) AC‐NPs can improve immunotherapy and the abscopal effect in B16F10 xenografts. Average tumor‐growth curves of unirradiated (secondary) tumors (b) and survival curves (c). (d,e) TDPA‐coated AC‐NPs enhance the efficacy of immunotherapy based on cancer vaccination. Average tumor‐growth curves (d) and survival curves (e). (Reprinted with permission from Min et al. (). Copyright 2017 Springer Nature)
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Nanoscale liposomal polymeric gels (nLGs) releasing TGF‐β inhibitor and IL‐2 sustainably. Experiment on animal models showed efficacy of nGLs. (a) In the first step of synthesis, methacrylate‐f‐CD was used to solubilize the TGF‐β inhibitor (SB505124). (b) In the second step, nLGs were formulated from lyophilized liposomes loaded with biodegradable crosslinking polymer, acrylated‐CD‐SB505 complex, and IL‐2 cytokine. (c) Plot of tumor area versus time (Day 0 was the day of tumor cell injection). Red arrows indicate treatments (via intratumoral injection). (d) Survival plot of mice from the same study given in c. Red arrows denote treatment days. (e) Survival plot of mice after systemic therapy. Red arrows denote treatment days. (Reprinted with permission from J. Park et al. (). Copyright 2012 Springer Nature)
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