title: Supramolecular PEGylated Dendritic Systems as pH/Redox Dual-Responsive Theranostic Nanoplatforms for Platinum Drug Delivery and NIR Imaging.
abstract: Recently, self-assembling small dendrimers into supramolecular dendritic systems offers an alternative strategy to develop multifunctional nanoplatforms for biomedical applications. We herein report a dual-responsive supramolecular PEGylated dendritic system for efficient platinum-based drug delivery and near-infrared (NIR) tracking. With a refined molecular/supramolecular engineering, supramolecular dendritic systems were stabilized by bioreducible disulfide bonds and endowed with NIR fluorescence probes, and PEGylated platinum derivatives coordinated onto the abundant peripheral groups of supramolecular dendritic templates to generate pH/redox dual-responsive theranostic supramolecular PEGylated dendritic systems (TSPDSs). TSPDSs markedly improved the pharmacokinetics and biodistribution of platinum-based drugs, owing to their stable nanostructures and PEGylated shells during the blood circulation. Tumor intracellular environment (low pH value and high glutathione concentration) could trigger the rapid disintegration of TSPDSs due to acid-labile coordination bonds and redox-cleavable disulfide linkages, and then platinum-based drugs were delivered into the nuclei to exert antitumor activity. In vivo antitumor treatments indicated TSPDSs not only provided high antitumor efficiency which was comparable to clinical cisplatin, but also reduced renal toxicity of platinum-based drugs. Moreover, NIR fluorescence of TSPDSs successfully visualized in vitro and in vivo fate of nanoplatforms and disclosed the intracellular platinum delivery and pharmacokinetics. These results confirm tailor-made supramolecular dendritic system with sophisticated nanostructure and excellent performance is a promising candidate as smart theranostic nanoplatforms.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Yunkun
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Xu
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: He
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, Sichuan, China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005456:Fluorescent Dyes / Q000032:analysis*; D064593:Heterografts; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007259:Infrared Rays; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010084:Oxidation-Reduction; D010984:Platinum / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D010984:Platinum
keywords: near-infrared imaging; pH and redox sensitivity; platinum delivery; supramolecular dendritic systems; theranostic nanoplatform