纳米凝胶
化学免疫疗法
癌症研究
三磷酸腺苷
化学
腺苷
癌症
纳米技术
药理学
材料科学
医学
免疫疗法
药物输送
内科学
生物化学
作者
Feiran Zhang,Jingwen Dong,Kan Huang,Bin Duan,Chenzi Li,Ruoxi Yang,Jing Li,Feng Zhi,Zhanwei Zhou,Minjie Sun
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-09-28
卷期号:17 (19): 18805-18817
被引量:1
标识
DOI:10.1021/acsnano.3c03386
摘要
Pathophysiological barriers in "cold" tumors seriously limit the clinical outcomes of chemoimmunotherapy. These barriers distribute in a spatial order in tumors, including immunosuppressive microenvironment, overexpressed chemokine receptors, and dense tumor mesenchyme, which require a sequential elimination in therapeutics. Herein, we reported a "dominolike" barriers elimination strategy by an intratumoral ATP supersensitive nanogel (denoted as BBLZ-945@PAC–PTX) for enhanced chemoimmunotherapy. Once it has reached the tumor site, BBLZ-945@PAC–PTX nanogel undergoes supersensitive collapse triggered by adenosine triphosphate (ATP) in perivascular regions and releases BLZ-945 conjugated albumin (BBLZ-945) to deplete tumor-associated macrophages (TAMs). Deeper spatial penetration of shrunk nanogel (PAC–PTX) could not only block CXCR4 on the cell membrane to decrease immunosuppressive cell recruitment but also internalize into tumor cells for tumor-killing and T cell priming. The strategy of "dominolike" barriers elimination in tumors enables immune cell infiltration for a potentiated immune response and offers a high-responsive treatment opinion for chemoimmunotherapy.
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