肿瘤微环境
药品
化疗
癌症研究
药物输送
免疫系统
药理学
阿霉素
医学
免疫学
化学
内科学
有机化学
作者
Jiahe Wu,Teng Ma,Manning Zhu,Jiafu Mu,Tianchen Huang,Donghang Xu,Nengming Lin,Jianqing Gao
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-02-09
被引量:5
标识
DOI:10.1021/acsnano.3c12694
摘要
The limited therapeutic outcomes and severe systemic toxicity of chemotherapy remain major challenges to the current clinical antitumor therapeutic regimen. Tumor-targeted drug delivery that diminishes the undifferentiated systemic distribution is a practical solution to ameliorating systemic toxicity. However, the tumor adaptive immune microenvironment still poses a great threat that compromises the therapeutic efficacy of chemotherapy by promoting the tolerance of the tumor cells. Herein, a pluripotential neutrophil-mimic nanovehicle (Neutrosome(L)) composed of an activated neutrophil membrane-incorporated liposome is proposed to modulate the immune microenvironment and synergize antitumor chemotherapy. The prominent tumor targeting capability inherited from activated neutrophils and the improved tumor penetration ability of Neutrosome(L) enable considerable drug accumulation in tumor tissues (more than sixfold that of free drug). Importantly, Neutrosome(L) can modulate the immune microenvironment by restricting neutrophil infiltration in tumor tissue, which may be attributed to the neutralization of inflammatory cytokines, thus potentiating antitumor chemotherapy. As a consequence, the treatment of cisplatin-loaded Neutrosome(L) performs prominent tumor suppression effects, reduces systemic drug toxicity, and prolongs the survival period of tumor-bearing mice. The pluripotential neutrophil-mimic nanovehicle proposed in this study can not only enhance the tumor accumulation of chemotherapeutics but also modulate the immune microenvironment, providing a compendious strategy for augmented antitumor chemotherapy.
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