Cancer-specific calcium nanoregulator suppressing the generation and circulation of circulating tumor cell clusters for enhanced anti-metastasis combinational chemotherapy  

作　　者：Dan Li Yingli Wang Chang Li Qiu Wang Bingjun Sun Haotian Zhang Zhonggui He Jin Sun 

机构地区：[1]Department of Pharmaceutics,Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]School of Life Science and Biopharmaceutics,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第10期3262-3271,共10页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China(No.81773656);Liaoning Revitalization Talents Program(No.XLYC1808017,China);Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454,China)。

摘　　要：Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death.Moreover,circulating tumor cell(CTC)clusters play a pivotal role in tumor metastasis.Herein,we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin(DIG)and doxorubicin(DOX)co-encapsulated PLGA nanoparticles(CPDDs).CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation.Intriguingly,CPDDs induce the accumulation of intracellular Ca^(2+) by inhibiting Na^(+)/K^(+)-ATPase,which help restrain cellecell junctions to disaggregate CTC clusters.Meanwhile,CPDDs suppress the epithelialemesenchymal transition(EMT)process,resulting in inhibiting tumor cells escape from the primary site.Moreover,the combination of DOX and DIG at a mass ratio of 5:1 synergistically induces the apoptosis of tumor cells.In vitro and in vivo results demonstrate that CPDDs not only effectively inhibit the generation and circulation of CTC clusters,but also precisely target and eliminate primary tumors.Our findings present a novel approach for anti-metastasis combinational chemotherapy.

关 键 词：Cell-cell junctions DIGOXIN DOXORUBICIN Homologous targeting Circulating tumor cell clusters Epithelial-mesenchymal transition Breast cancer Lung metastasis 

分 类 号：R730.5[医药卫生—肿瘤]