Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis  

作　　者：Haili Hu Weiwei Zhang Lei Lei Fan Tong Huilin Zhang Yiwei Zhang Wenqin Yang Yilu Tang Ruyi Lin Xue Xia Jiamei Li Shiyong Song Huile Gao 

机构地区：[1]Key Laboratory of Drug Targeting and Drug Delivery Systems,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [2]School of Pharmacy,Henan University,Kaifeng 475004,China [3]Department of Public Health,Chengdu Medical College,Chengdu 610500,China

出　　处：《Chinese Chemical Letters》2024年第3期406-414,共9页中国化学快报（英文版）

基　　金：supported by National Natural Science Foundation of China(No.82173762);Research Funds of Sichuan Science and Technology Department(Nos.2022JDJQ0050,2022YFS0334);111 Project(No.B18035)。

摘　　要：The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer cells.Worse still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune cells.To solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor site.Upon irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ICD.Moreover,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic tumors.In vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.

关 键 词：Targeted drug delivery system Hollow copper sulfide nanoparticles Photothermal therapy Hyaluronic acid Breast cancer ANTI-METASTASIS 

分 类 号：R737.9[医药卫生—肿瘤] TB383.1[医药卫生—临床医学] TQ460.1[一般工业技术—材料科学与工程]