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Nanoengineered drug delivery in cancer immunotherapy for overcoming immunosuppressive tumor microenvironment

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Abstract

Almost like a living being in and of itself, tumors actively interact with and modify their environment to escape immune responses. Owing to the pre-formation of cancer-favorable microenvironment prior to anti-cancer treatment, the numerous attempts that followed propose limited efficacy in oncology. Immunogenicity by activation of immune cells within the tumor microenvironment or recruitment of immune cells from nearby lymph nodes is quickly offset as the immunosuppressive environment, rapidly converting immunogenic cells into immune suppressive cells, overriding the immune system. Tumor cells, as well as regulatory cells, namely M2 macrophages, Treg cells, and MDSCs, derived by the immunosuppressive environment, also cloak from potential anti-tumoral factors by directly or indirectly secreting cytokines, such as IL-10 and TGF-β, related to immune regulation. Enzymes and other metabolic or angiogenetic constituents — VEGF, IDO1, and iNOS — are also employed directed for anti-cancer immune cell malfunctioning. Therefore, the conversion of “cold” immunosuppressive environment into “hot” immune responsive environment is of paramount importance, bestowing the advances in the field of cancer immunotherapy the opportunity to wholly fulfill its intended purpose. This paper reviews the mechanisms by which tumors wield to exercise immune suppression and the nanoengineered delivery strategies being developed to overcome this suppression.

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Acknowledgements

The authors are thankful to National Research Foundation (NRF) of Korea government for the financial support (grant numbers 2020R1A2C3006888 and SRC-2017R1A5A1014560).

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This work was supported by National Research Foundation (NRF) grants funded by the Korean government (grant numbers 2020R1A2C3006888 and SRC-2017R1A5A1014560).

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  1. Sei Hyun Park, Ryounho Eun, and Janghun Heo contributed equally to this work.

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  1. SKKU Advanced Institute of Nanotechnology (SAINT), Department of Nano Science and Technology, Department of Nano Engineering, School of Chemical Engineering, and Biomedical Institute for Convergence at SKKU, Sungkyunkwan University (SKKU), Suwon, Gyeonggi-Do, 16419, Republic of Korea

    Sei Hyun Park, Ryounho Eun, Janghun Heo & Yong Taik Lim

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All authors contributed to conceptualization of the work. Sei Hyun Park contributed to idea design, Ryounho Eun contributed to figure design, Janghun Heo wrote the draft of the manuscript, and Yong Taik Lim critically revised the draft. All authors read and approved the final manuscript.

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Park, S.H., Eun, R., Heo, J. et al. Nanoengineered drug delivery in cancer immunotherapy for overcoming immunosuppressive tumor microenvironment. Drug Deliv. and Transl. Res. 13, 2015–2031 (2023). https://doi.org/10.1007/s13346-022-01282-8

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