Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells.
Dual responsive nanoparticles are developed for co-delivery of multiple anticancer drugs to target the drug resistance mechanisms of cancer stem-like cells (CSCs). The nanoparticles consist of four polymers approved by the Food and Drug Administration (FDA) for medical use: Poly(d,l-lactide-co-glycolide) (PLGA), Pluronic F127 (PF127), chitosan, and hyaluronic acid (HA). By combining PLGA and PF127 together, more stable and uniform-sized nanoparticles can be obtained than using PLGA or PF127 alone. The HA is used for not only actively targeting CSCs to reduce their drug resistance due to dormancy (i.e., slow metabolism), but also replacing the commonly used poly(vinyl alcohol) as a stabilizing agent to synthesize the nanoparticles using the double-emulsion approach and to allow for acidic pH-triggered drug release and thermal responsiveness. Besides minimizing drug efflux from CSCs, the nanoparticles encapsulated with doxorubicin hydrochloride (DOX, hydrophilic) and irinotecan (CPT, hydrophobic) to inhibit the activity of topoisomerases II and I, respectively, can fight against the CSC drug resistance associated with their enhanced DNA repair and anti-apoptosis. Ultimately, the two drugs-laden nanoparticles can be used to efficiently destroy the CSCs both in vitro and in vivo with up to ∼500 times of enhancement compared to the simple mixture of the two drugs.
['Wang|Hai|H|', 'Agarwal|Pranay|P|', 'Zhao|Shuting|S|', 'Xu|Ronald X|RX|', 'Yu|Jianhua|J|', 'Lu|Xiongbin|X|', 'He|Xiaoming|X|']
D000818:Animals D000970:Antineoplastic Agents D002166:Camptothecin D045744:Cell Line, Tumor D048271:Chitosan D004317:Doxorubicin D016503:Drug Delivery Systems D065546:Drug Liberation D019008:Drug Resistance, Neoplasm D004705:Endocytosis D006801:Humans D006820:Hyaluronic Acid D006863:Hydrogen-Ion Concentration D042541:Intracellular Space D000077146:Irinotecan D019344:Lactic Acid D008297:Male D008819:Mice, Nude D053758:Nanoparticles D014411:Neoplastic Stem Cells D020442:Poloxamer D011100:Polyglycolic Acid D000077182:Polylactic Acid-Polyglycolic Acid Copolymer D018874:Spheroids, Cellular D014018:Tissue Distribution
Co-delivery Cancer stem-like cell Drug resistance Topoisomerase CD44