title: Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor.
abstract: Chemotherapeutic drugs frequently encounter multiple drug resistance in the field of cancer therapy. The strategy has been explored with limited success for the ablation of drug-resistant tumor via intravenous administration. In this work, the rationally designed light-triggered nanoparticles with multipronged physicochemical and biological features are developed to overcome cisplatin resistance via the assembly of Pt(IV) prodrug and cyanine dye (Cypate) within the copolymer for efficient ablation of cisplatin-resistant tumor. The micelles exhibit good photostability, sustained release, preferable tumor accumulation, and enhanced cellular uptake with reduced efflux on both A549 cells and resistant A549R cells. Moreover, near-infrared light not only triggers the photothermal effect of the micelles for remarkable photothermal cytotoxicity, but also leads to the intracellular translocation of the micelles and reduction-activable Pt(IV) prodrug into cytoplasm through the lysosomal disruption, as well as the remarkable inhibition on the expression of a drug-efflux transporter, multidrug resistance-associated protein 1 (MRP1) for further reversal of drug resistance of A549R cells. Consequently, the multipronged effects of light-triggered micelles cause synergistic cytotoxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without regrowth. The multipronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Hengte
authors.initials: H
authors.lastname: Ke
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Guo
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Zhengqing
authors.initials: Z
authors.lastname: Guo
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Zhishen
authors.initials: Z
authors.lastname: Ge
authors.affiliation: National Engineering Research Center for Nanomedicine, and College of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, Hubei 430074, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, and College of Pharmaceutical Sciences, Soochow University , Suzhou, Jiangsu 215123, China.|School for Radiological & Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Huabing
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D010984:Platinum / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011422:Propionates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; C000604523:Cypate; D003692:Delayed-Action Preparations; D005456:Fluorescent Dyes; D007211:Indoles; D008823:Micelles; D011355:Prodrugs; D011422:Propionates; D010984:Platinum; D002945:Cisplatin
keywords: cisplatin resistance; micelles; multipronged effect; synergistic therapy; tumor ablation