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Transforming Complexity to Simplicity: Protein-Like Nanotransformer for Improving Tumor Drug Delivery Programmatically

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journal contribution
posted on 17.04.2020, 12:04 by Hui Xiong, Zihan Wang, Cheng Wang, Jing Yao
It was difficult for nanodrugs to simultaneously meet the contradictory requirements of prolonged circulation time, augmented cellular uptake, rapid lysosome escape, precise drug release, and tumor penetration in tumor drug delivery. We prepared a nanotransformer (DTIG) through assembling doxorubicin, tannic acid, and indocyanine green to overcome this dilemma. Hydrophilic DTIG showed prolonged blood circulation time. Besides, DTIG could be efficiently internalized by tumor cells through transforming into hydrophobic particles in an acidic tumor microenvironment. Subsequently, oversized hydrophobic particles were further formed in acidic lysosomes to escape from it through rupturing the lysosome. These hydrophobic DTIGs could rapidly revert to a smaller hydrophilic nanoassembly and release the payloads in cytoplasm. Similar to denaturation and renaturation of protein, these high-efficiency instantaneous transformations were activated by proton. Besides, photothermal therapy of DTIG promoted drug penetration efficiency in tumor. This optimized drug delivery process of DTIG finally offered potent antitumor efficacy and an obvious advantage on prognosis.