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Hydrazide-manganese coordinated multifunctional nanoplatform for potentiating immunotherapy in hepatocellular carcinoma.
Hou, Guanghui; Qian, Junmin; Guo, Min; Xu, Weijun; Wang, Jinlei; Wang, Yaping; Suo, Aili.
Afiliação
  • Hou G; State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
  • Qian J; State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: jmqian@mail.xjtu.edu.cn.
  • Guo M; State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
  • Xu W; State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
  • Wang J; State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
  • Wang Y; State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
  • Suo A; Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: ailisuo@mail.xjtu.edu.cn.
J Colloid Interface Sci ; 628(Pt B): 968-983, 2022 Dec 15.
Article em En | MEDLINE | ID: mdl-36037718
ABSTRACT
Immune checkpoint blockade (ICB)-based immunotherapy is a revolutionary therapeutic strategy for hepatocellular carcinoma (HCC). However, tumor immune tolerance and escape severely restrict the therapeutic efficacy of ICB therapy. It is urgent to explore new strategies to potentiate ICB therapy in HCC. Herein, we developed manganese oxide-crosslinked bovine albumin/hyaluronic acid nanoparticles (BHM) by an innovative hydrazide-manganese coordination and desolvation process. Successive loading of doxorubicin (DOX) and indocyanine green (ICG) was achieved via hydrazone linkage and electrostatic interactions, respectively, obtaining DOX/ICG-coloaded BHM nanoplatform (abbreviated as BHMDI). The BHMDI nanoplatform exhibited a high drug content (>46%) and pH/reduction dual-responsive drug release behavior. The nanoplatform could efficiently alleviate tumor hypoxia by catalytic decomposition of intracellular H2O2 to O2 and significantly improve BHMDI-based photodynamic chemotherapy efficacy. The BHMDI nanoplatform downregulated the proportion of alternatively activated (M2) macrophages in tumors and simultaneously induced immunogenic death of HCC cells, thus promoting the maturation of dendritic cells and ensuing priming of CD4+ and CD8+ T cells. Importantly, programmed death-1 (PD-1) blockade in combination with BHMDI nanoplatform not only eradicated primary tumors but inhibited tumor recurrence, abscopal tumor growth and lung metastasis of HCC by triggering robust systemic antitumor immunity. This work proved the feasibility of BHMDI-based photodynamic chemotherapy for potentiating PD-1 blockade immunotherapy by reversing hypoxic and immunosuppressive tumor microenvironment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Nanopartículas / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Nanopartículas / Neoplasias Hepáticas Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article