In vivo self-assembled drug nanocrystals for metastatic breast cancer all-stage targeted therapy

• Published in: Journal of controlled release Vol. 346; pp. 32 - 42
• Main Authors: Luo, Zimiao, Lu, Linwei, Xu, Weixia, Meng, Nana, Wu, Sunyi, Zhou, Jianfen, Xu, Qianzhu, Xie, Cao, Liu, Yu, Lu, Weiyue
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2022
• Subjects: All-stage targeted therapy; Drug nanocrystals; In vivo self-assembly; Metastatic breast cancer; Metastatic breast cancer; In vivo self-assembly; All-stage targeted therapy; Drug nanocrystals
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.03.058

Chemotherapy is still the mainstay treatment for metastatic triple-negative breast cancers (TNBC) currently in clinical practice. The unmet needs of chemotherapy for metastatic TNBC are mainly from the insufficient drug delivery and unavailable targeting strategy that thwart the whole progression of metastatic TNBC. The in vivo ligands-mediated active targeting efficiency is usually affected by protein corona. While, the protein corona-bridged natural targeting, in turn, provides a new way for specific drug delivery. Herein, we develop a novel metastatic progression-oriented in vivo self-assembled Cabazitaxel nanocrystals (CNC) delivery system (PC/CNC) through the CNC automatically absorbing functional plasma proteins (transferrin, apolipoprotein A-IV and apolipoprotein E) in vivo, aiming to achieve the simultaneously targeted delivery to primary tumors, circulating tumor cells and metastatic lesions. With the unique advantages of superhigh drug-loading and protein corona empowered active targeting properties to tumor cells, HUVECs, active-platelets and blood-brain barrier/blood-tumor barrier, the PC/CNC exhibits a significantly improved therapeutic effect in metastatic TNBC therapy compared with free drug and CNC-loaded liposomes. The PC/CNC was developed through CNC spontaneously absorbing functional plasma proteins in vivo. The PC/CNC hindered the progression of TNBC via the protein corona-mediated natural targeting delivery to primary tumors, CTCs and metastatic lesions [Display omitted]