纳微快报（英文）2021，Vol.13Issue(2)：144-161,18.
CaCO3-Assisted Preparation of pH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy
CaCO3?Assisted Preparation of pH?Responsive Immune?Modulating Nanoparticles for Augmented Chemo?Immunotherapy
摘要
Abstract
Due to the negative roles of tumor microenvironment (TME) in compromising therapeutic responses of various cancer thera-pies, 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 inhibi-tor 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 produc-tion of immunosuppressive kynurenine by inhibiting IDO1. Upon intra-venous 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 nano-particles, endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.关键词
CaCO3-assisted double emulsion/pH-responsiveness/Neutralization of acidic TME/Immunosuppressive tumor microenvironment modulation/Chemo-immunotherapyKey words
CaCO3-assisted double emulsion/pH-responsiveness/Neutralization of acidic TME/Immunosuppressive tumor microenvironment modulation/Chemo-immunotherapy引用本文复制引用
Yujie Zhu,Zhijuan Yang,Ziliang Dong,Yimou Gong,Yu Hao,Longlong Tian,Xianzhu Yang,Zhuang Liu,Liangzhu Feng..CaCO3-Assisted Preparation of pH-Responsive Immune-Modulating Nanoparticles for Augmented Chemo-Immunotherapy[J].纳微快报（英文）,2021,13(2):144-161,18.基金项目
This work was partially supported by the National Natural Science Foundation of China (51802209, 22077093, 51761145041, 51525203), the National Research Pro-grams from Ministry of Science and Technology (MOST) of China (2016YFA0201200), the Natural Science Foundation of Jiangsu Province (BK20180848), the Jiangsu Social Development Project (BE2019658), Collaborative Innovation Center of Suzhou Nano Science and Technology, and the 111 Program from the Ministry of Education of China. We also thank the website of app.Biorender. com for its assistance in the creation of schemes. （51802209, 22077093, 51761145041, 51525203）
