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Vol. 13 (2021)

CaCO3-Assisted Preparation of pH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy

https://doi.org/10.1007/s40820-020-00549-4
Yujie Zhu
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Zhijuan Yang
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Ziliang Dong
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Yimou Gong
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Yu Hao
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Longlong Tian
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Xianzhu Yang
Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, Guangdong, People’s Republic of China
Zhuang Liu
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Liangzhu Feng
Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China

Corresponding Author: Liangzhu Feng

lzfeng@suda.edu.cn

Nano-Micro Letters, Vol. 13 (2021), Article Number: 29

Abstract

Due to the negative roles of tumor microenvironment (TME) in compromising therapeutic responses of various cancer therapies, it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment. Herein, we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method, thereby enabling effective co-encapsulation of both doxorubicin (DOX), an immunogenic cell death (ICD) inducer, and alkylated NLG919 (aNLG919), an inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). The obtained DOX/aNLG919-loaded CaCO3 nanoparticles (DNCaNPs) are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1. Upon intravenous injection, such DNCaNPs show efficient tumor accumulation, improved tumor penetration of therapeutics and neutralization of acidic TME. As a result, those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+ cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells (Tregs), thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy & immunotherapy. This study presents a compendious strategy for construction of pH-responsive nanoparticles, endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.


Highlights:


1 CaCO3-assisted double emulsion method was developed to prepare pH-responsive nanoparticles enabling effective encapsulation of diverse molecules.
2 The introducing of CaCO3 could enable deep intratumoral penetration of therapeutic agents and effective neutralization of acidic tumor pH to favor the reverse of immunosuppressive tumor microenvironment (TME).
3 The reverse of immunosuppressive TME ascribing to NLG919-mediated IDO1 inhibition and CaCO3-mediated neutralization of acidic TME could collectively contribute to augmented chemo-immunotherapy of cancer.

Keywords

CaCO3-assisted double emulsion pH-responsiveness Neutralization of acidic TME Immunosuppressive tumor microenvironment modulation Chemo-immunotherapy
Zhu, Yujie, Zhijuan Yang, Ziliang Dong, Yimou Gong, Yu Hao, Longlong Tian, Xianzhu Yang, Zhuang Liu, and Liangzhu Feng. 2020. “CaCO3-Assisted Preparation of PH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy”. Nano-Micro Letters 13 (November):29. https://doi.org/10.1007/s40820-020-00549-4.
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