Co-delivery of docetaxel and bortezomib based on a targeting nanoplatform for enhancing cancer chemotherapy effects.

Nie, Junpeng; Cheng, Wei; Peng, Yunmei; Liu, Gan; Chen, Yuhan; Wang, Xusheng; Liang, Chaoyu; Tao, Wei; Wei, Yinping; Zeng, Xiaowei; Mei, Lin

Using facile polydopamine (PDA)-based surface modification and a pH-sensitive catechol-boronate binding mechanism, a novel drug delivery system was designed for the treatment of breast cancer. The system was able to achieve the following goals: active targeting, pH responsiveness,in vivoblood circulation for a prolonged period of time, and dual drug loading. After coating with PDA, the docetaxel (DTX)-loaded star-shaped copolymer cholic acid-poly(lactide-co-glycolide) nanoparticles (CA-PLGA@PDA/NPs) were functionalized with amino-poly(ethylene glycol)-folic acid (NH2-PEG-FA) and bortezomib (BTZ) to form the targeting composition, DTX-loaded CA-PLGA@PDA-PEG-FA BTZ/NPs. The novel NPs exhibited similar drug release characteristics compared to unfunctionalized CA-PLGA/NPs. Meanwhile, the incorporated NH2-PEG-FA contributed to active targeting which was illustrated by cellular uptake experiments and biodistribution studies. Moreover, the pH responsive binding between BTZ and PDA was demonstrated to be effective to release BTZ at the tumor acidic environment for synergistic action with DTX. Bothin vitrocytotoxicity andin vivoantitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FA BTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.

DOCETAXEL; BORTEZOMIB; BREAST cancer; BREAST cancer treatment; CANCER chemotherapy; DRUG delivery systems

Drug Delivery, 2017, Vol 24, Issue 1, p1124

1071-7544

Academic Journal

10.1080/10717544.2017.1362677