title: Visible light-induced crosslinking and physiological stabilization of diselenide-rich nanoparticles for redox-responsive drug release and combination chemotherapy.
abstract: Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine. Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG-b-PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light-induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments. In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy.
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
authors.forename: Shaodong
authors.initials: S
authors.lastname: Zhai
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China. Electronic address: xlhu@scnu.edu.cn.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China. Electronic address: xingda@scnu.edu.cn.
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000528:radiation effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004355:Drug Stability; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D010084:Oxidation-Reduction / Q000528:radiation effects; D018036:Selenium Compounds / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D018036:Selenium Compounds; D004317:Doxorubicin; D002166:Camptothecin
keywords: Combination chemotherapy; Crosslinking; Diselenide bonds; Redox responsiveness; Visible light