Charge-Convertible Carbon Dots for Imaging-Guided Drug Delivery with Enhanced in Vivo Cancer Therapeutic Efficiency

纳米载体 体内 前药 肿瘤微环境 药物输送 生物物理学 化学 纳米技术 材料科学 癌细胞 癌症研究 癌症 生物化学 医学 肿瘤细胞 生物技术 内科学 生物
作者
Tao Feng,Xiangzhao Ai,Guanghui An,Piaoping Yang,Yanli Zhao
出处
期刊:ACS Nano [American Chemical Society]
卷期号:10 (4): 4410-4420 被引量:584
标识
DOI:10.1021/acsnano.6b00043
摘要

Carbon dots (CDs) are remarkable nanocarriers due to their promising optical and biocompatible capabilities. However, their practical applicability in cancer therapeutics is limited by their insensitive surface properties to complicated tumor microenvironment in vivo. Herein, a tumor extracellular microenvironment-responsive drug nanocarrier based on cisplatin(IV) prodrug-loaded charge-convertible CDs (CDs–Pt(IV)@PEG-(PAH/DMMA)) was developed for imaging-guided drug delivery. An anionic polymer with dimethylmaleic acid (PEG-(PAH/DMMA)) on the fabricated CDs–Pt(IV)@PEG-(PAH/DMMA) could undergo intriguing charge conversion to a cationic polymer in mildly acidic tumor extracellular microenvironment (pH ∼ 6.8), leading to strong electrostatic repulsion and release of positive CDs–Pt(IV). Importantly, positively charged nanocarrier displays high affinity to negatively charged cancer cell membrane, which results in enhanced internalization and effective activation of cisplatin(IV) prodrug in the reductive cytosol. The in vitro experimental results confirmed that this promising charge-convertible nanocarrier possesses better therapeutic efficiency under tumor extracellular microenvironment than normal physiological condition and noncharge-convertible nanocarrier. The in vivo experiments further demonstrated high tumor-inhibition efficacy and low side effects of the charge-convertible CDs, proving its capability as a smart drug nanocarrier with enhanced therapeutic effects. The present work provides a strategy to promote potential clinical application of CDs in the cancer treatment.
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