Статья

Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy

Chunai GongDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaJing TianDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaZhuo WangDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaYuan GaoDepartment of Clinical Pharmacy and Pharmaceutical Management, School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of ChinaXin WuDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaXueying DingDepartment of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, People's Republic of ChinaLei QiangDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaGuorui LiDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaZhimin HanDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of ChinaYongfang YuanDepartment of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People's Republic of China. [email protected]Shen GaoDepartment of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of China. [email protected]

2019en

ABI

Аннотация

Exosomes (Exo) hold great promise as endogenous nanocarriers that can deliver biological information between cells. However, Exo are limited in terms of their abilities to target specific recipient cell types. We developed a strategy to isolate Exo exhibiting increased binding to integrin αvβ3. Binding occurred through a modified version of a disintegrin and metalloproteinase 15 (A15) expressed on exosomal membranes (A15-Exo), which facilitated co-delivery of therapeutic quantities of doxorubicin (Dox) and cholesterol-modified miRNA 159 (Cho-miR159) to triple-negative breast cancer (TNBC) cells, both in vitro and in vivo. The targeted A15-Exo were derived from continuous protein kinase C activation in monocyte-derived macrophages. These cell-derived Exo displayed targeting properties and had a 2.97-fold higher production yield. In vitro, A15-Exo co-loaded with Dox and Cho-miR159 induced synergistic therapeutic effects in MDA-MB-231 cells. In vivo, miR159 and Dox delivery in a vesicular system effectively silenced the TCF-7 gene and exhibited improved anticancer effects, without adverse effects. Therefore, our data demonstrate the synergistic efficacy of co-delivering miR159 and Dox by targeted Exo for TNBC therapy.

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Идентификаторы

DOI: 10.1186/s12951-019-0526-7

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar