期刊
DRUG DELIVERY
卷 24, 期 1, 页码 1124-1138出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2017.1362677
关键词
Cancer nanotechnology; polydopamine; pH-response; co-delivery; targeting nanoplatform
资金
- Guangdong Natural Science Foundation for Distinguished Young Scholar [2014A030306036]
- Science and Technology Planning Project of Guangdong Province [2016A020217001]
- Natural Science Foundation of Guangdong Province [2015A030313848, 2016A030310023]
- Science, Technology and Innovation Commission of Shenzhen Municipality [JCYJ2016053 1195129079, JCYJ201603011 52300347, JCYJ20170412095722235, JCYJ20160429182415013, JCYJ20140417115840267]
- Guangdong Special Support Program [201428030]
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 vivo blood 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-FAthornBTZ/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. Both in vitro cytotoxicity and in vivo antitumor studies demonstrated that the novel nanoplatform exhibited the most suitable therapeutic effects. Taken together, the versatile PDA modified DTX-loaded CA-PLGA@PDA-PEG-FAthornBTZ/NPs offered a promising chemotherapeutic strategy for enhancing breast cancer treatment.
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