期刊
ACTA PHARMACEUTICA SINICA B
卷 11, 期 10, 页码 3262-3271出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2021.04.009
关键词
KEY WORDS Cell-cell junctions; Digoxin; Doxorubicin; Homologous targeting; Circulating tumor cell clusters; Epithelial-mesenchymal transition; Breast cancer; Lung metastasis
资金
- National Natural Science Foundation of China [81773656]
- Liaoning Revitalization Talents Pro-gram [XLYC1808017]
- Shenyang Youth Science and Technology Innovation Talents Program [RC190454]
The study introduces cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters, providing a novel approach for anti-metastasis combinational chemotherapy.
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 Ca2 thorn by inhibiting Na thorn /K thorn -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. (c) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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