Spatially targeting of tumor-associated macrophages and cancer cells for suppression of spontaneously metastatic tumor
作者机构：Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China
出 版 物：《Nano Research》 (纳米研究（英文版）)
年 卷 期：2022年第15卷第4期
页 面：3446-3457页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：spatial distribution tumor-associated macrophage immunogenic cell death anti-tumor immunity cancer metastasis
摘 要：The interaction between cancer cells and M2 tumor-associated macrophages(M2-TAMs)facilitates tumor growth and ***,cancer cells and M2-TAMs have different spatial distribution patterns,which requires distinct drug delivery ***,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 ***,we found iRGD-HD induced cancer cells undergoing immunogenic cell death to enhance tumor infiltration of CD8^(+)T ***,AAN-Lip-Rego efficiently repolarized TAMs from M2 into M1 to alleviate tumor immunosuppression,thus reviving CD8^(+)T ***,the repolarization of TAMs led to dramatic downregulation of prometastatic factors expressed on cancer *** 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.
维普期刊数据库