Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor.
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.
['Li|Yanli|Y|', 'Deng|Yibin|Y|', 'Tian|Xin|X|', 'Ke|Hengte|H|', 'Guo|Miao|M|', 'Zhu|Aijun|A|', 'Yang|Tao|T|', 'Guo|Zhengqing|Z|', 'Ge|Zhishen|Z|', 'Yang|Xiangliang|X|', 'Chen|Huabing|H|']
D000818:Animals D000970:Antineoplastic Agents D045744:Cell Line, Tumor D002945:Cisplatin D003692:Delayed-Action Preparations D019008:Drug Resistance, Neoplasm D005260:Female D005456:Fluorescent Dyes D006801:Humans D007211:Indoles D008027:Light D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D008823:Micelles D053758:Nanoparticles D009369:Neoplasms D010984:Platinum D011355:Prodrugs D011422:Propionates
cisplatin resistance micelles multipronged effect synergistic therapy tumor ablation