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
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（10）
• 所属期刊栏目: Original articles
• 页码范围: 3262-3271
• 页数: 10页
• 语种: 英文

摘要

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death.More-over,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 can-cer 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 Ca2+ by inhibit-ing Na+/K+-ATPase,which help restrain cell--cell junctions to disaggregate CTC clusters.Meanwhile,CPDDs suppress the epithelial-mesenchymal 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.