癌症研究
癌细胞
转移
癌症
肿瘤微环境
生物
医学
内科学
肿瘤细胞
作者
Minglu Zhou,Dandan Xie,Zhou Zhou,Lian Li,Yuan Huang
出处
期刊:Nano Research
[Springer Nature]
日期:2021-12-26
卷期号:15 (4): 3446-3457
被引量:1
标识
DOI:10.1007/s12274-021-3976-9
摘要
The interaction between cancer cells and M2 tumor-associated macrophages (M2-TAMs) facilitates tumor growth and metastasis. However, cancer cells and M2-TAMs have different spatial distribution patterns, which requires distinct drug delivery strategies. Herein, based on different tumor-penetrating ability of nanocarriers, we developed a combinatory strategy that consists of a TAMs-targeting liposome (alanine-alanine-asparagine (AAN)-Lip-regorafenib (Rego)) and a cancer cells-targeting copolymer (internalizing RGD modified with N-(2-hydroxypropyl) methacrylamide-doxorubicin (iRGD-HD)). Our study confirmed AAN-Lip-Rego accumulated at perivascular sites where M2-TAM is located, while iRGD-HD penetrated into deep site of tumor to enter cancer cells. Thereafter, we found iRGD-HD induced cancer cells undergoing immunogenic cell death to enhance tumor infiltration of CD8+ T cells. Meanwhile, AAN-Lip-Rego efficiently repolarized TAMs from M2 into M1 to alleviate tumor immunosuppression, thus reviving CD8+ T cells. Moreover, the repolarization of TAMs led to dramatic downregulation of prometastatic factors expressed on cancer cells. As a result, such combinatory approach elicited robust antitumor immune responses and generated considerable anti-tumor and anti-metastasis efficacy to markedly inhibit primary tumor and spontaneous lung metastasis.
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