Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency

Miao Kong^{1, 2}, Jiamin Tang³, Qi Qiao¹, Tingting Wu¹, Yan Qi¹, Songwei Tan^{1, 4}, Xueqin Gao¹, Zhiping Zhang^{1, 4, 5✉}

1. Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China;
2. Department of Pharmacy, Sanmenxia Central Hospital, Sanmenxia 472000, China;
3. China Three Gorges University, Yichang 443002, China;
4. National Engineering Research Center for Nanomedicine;
5. Hubei Engineering Research Center for Novel Drug Delivery System, Huazhong University of Science and Technology, Wuhan 430030, China.

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Citation:
Kong M, Tang J, Qiao Q, Wu T, Qi Y, Tan S, Gao X, Zhang Z. Biodegradable Hollow Mesoporous Silica Nanoparticles for Regulating Tumor Microenvironment and Enhancing Antitumor Efficiency. Theranostics 2017; 7(13):3276-3292. doi:10.7150/thno.19987. Available from https://www.thno.org/v07p3276.htm

Abstract

There is accumulating evidence that regulating tumor microenvironment plays a vital role in improving antitumor efficiency. Herein, to remodel tumor immune microenvironment and elicit synergistic antitumor effects, lipid-coated biodegradable hollow mesoporous silica nanoparticle (dHMLB) was constructed with co-encapsulation of all-trans retinoic acid (ATRA), doxorubicin (DOX) and interleukin-2 (IL-2) for chemo-immunotherapy. The nanoparticle-mediated combinational therapy provided a benign regulation on tumor microenvironment through activation of tumor infiltrating T lymphocytes and natural killer cells, promotion of cytokines secretion of IFN-γ and IL-12, and down-regulation of immunosuppressive myeloid-derived suppressor cells, cytokine IL-10 and TGF-β. ATRA/DOX/IL-2 co-loaded dHMLB demonstrated significant tumor growth and metastasis inhibition, and also exhibited favorable biodegradability and safety. This nanoplatform has great potential in developing a feasible strategy to remodel tumor immune microenvironment and achieve enhanced antitumor effect.

Keywords: nanoparticles, tumor microenvironment, immunosuppression, drug delivery, cancer treatment.