期刊
ACS APPLIED MATERIALS & INTERFACES
卷 14, 期 44, 页码 49542-49554出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c14448
关键词
programmed death ligand-1; tumor-associated macrophages; nanodrug; hepatocellular carcinoma; immune microenvironment
资金
- National Natural Science Foundation of China [82072033, 82170405]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515010380, 2019A1515011311]
- 5010 Project of Clinical medicine Research Sun Yat-sen University [2018011]
- Key Areas Research and Development Program of Guangzhou [202007020006]
In this study, a nanodrug was designed to regulate the tumor microenvironment and activate antitumor immunity by co-delivering an NF-KB inhibitor and a PD-L1 antibody. This provides a potential strategy to improve the efficiency of ICB-based treatment for HCC.
Immune checkpoint blockade (ICB) utilizing programmed death ligand-1 (PD-L1) antibody is a promising treatment strategy in solid tumors. However, in fact, more than half of hepatocellular carcinoma (HCC) patients are unresponsive to PD-L1 based ICB treatment due to multiple immune evasion mechanisms such as the hyperactivation of inflammation pathway, excessive tumor-associated macrophages (TAMs) infiltration, and insufficient infiltration of T cells. Herein, an inflammation-regulated nanodrug was designed to codeliver NF -KB inhibitor curcumin and PD-L1 antibody to reprogram the tumor microenvironment (TME) and activate antitumor immunity. The nanodrug accumulated in TME by an enhanced permeability and retention effect, where it left antibody to block PD-L1 on the membrane of tumor cells and TAMs due to pH-responsiveness. Simultaneously, a new curcumin-encapsulated nanodrug was generated, which was easily absorbed by either tumor cells or TAMs to inhibit the nuclear factor kappa-B (NF -KB) signal and related immunosuppressive genes. The inflammation-regulated nanodrug possessed good biocompatibility. Simultaneously, it reprogrammed TME effectively and exhibited an effective anticancer effect in immunocompetent mice. Overall, this study provided a potent strategy to improve the efficiency of ICB-based treatment for HCC.
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