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

• 作者: Liangzhu Feng Longlong Tian Xianzhu Yang Yimou Gong Yu Hao Yujie Zhu Zhijuan Yang Zhuang Liu Ziliang Dong
• 来源期刊: 纳微快报（英文）
• 年，卷（期）: 2021,（2）
• 页码范围: 144-161
• 页数: 18页
• 语种: 英文

摘要

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.