Charge-Convertible Carbon Dots for Imaging Guided Drug Delivery with Enhanced in Vivo Cancer Therapeutic Efficiency
Charge-Convertible Carbon Dots for Imaging Guided Drug Delivery with Enhanced in Vivo Cancer Therapeutic Efficiency
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DOI：
10.1021/acsnano.6b00043
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发表时间：
2016-04-01
期刊：
影响因子：
17.1
通讯作者：
Zhao, Yanli
中科院分区：
文献类型：
--
作者：
Feng, Tao;Ai, Xiangzhao;Zhao, Yanli
碳点(Cd)是一种引人注目的纳米载体，因为它们具有良好的光学和生物相容性。然而，由于它们对体内复杂的肿瘤微环境不敏感，限制了它们在癌症治疗中的实际应用。因此，基于顺铂(IV)前药载药电荷可转换CDS的肿瘤细胞外微环境响应性药物纳米载体(CDS-铂(IV)@聚乙二醇-(PAH/DMMA))被开发用于成像导向给药。在弱酸性的肿瘤细胞外微环境(pH约6.8)中，聚乙二醇二甲基马来酸阴离子聚合物(PEG-(PAH/DMMA))在CDS-铂(IV)@聚乙二醇(PAH/DMMA)表面可以发生有趣的电荷转化为阳离子聚合物，导致较强的静电斥力和阳离子CDS-铂(IV)的释放。重要的是，带正电的纳米载体对带负电的癌细胞膜具有很高的亲和力，这导致顺铂(IV)前药在还原胞浆中的内化和有效激活。体外实验结果证实，在肿瘤细胞外微环境下，这种有前景的电荷可转换纳米载体比正常生理条件下和非电荷可转换纳米载体具有更好的治疗效果。体内实验进一步证明了电荷可转换CD的高抑瘤效率和低副作用，证明了其作为一种智能药物纳米载体的能力，并增强了治疗效果。本工作为促进CDS在癌症治疗中的潜在临床应用提供了一种策略。
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 similar to 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.