Label-Free Fluorescent Poly(amidoamine) Dendrimer for Traceable and Controlled Drug Delivery
Label-Free Fluorescent Poly(amidoamine) Dendrimer for Traceable and Controlled Drug Delivery
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用于可追踪和受控药物输送的无标记荧光聚（酰胺基胺）树枝状聚合物
DOI：
10.1021/acs.biomac.9b00494
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发表时间：
2019
影响因子：
6.2
通讯作者：
Shi Bingyang
中科院分区：
文献类型：
--
作者：
Wang Guoying;Fu Libing;Walker Adam;Chen Xianfeng;Lovejoy David B;Hao Mingcong;Lee Albert;Chung Roger;Rizos Helen;Irvine Mal;Zheng Meng;Liu Xiuhua;Lu Yiqing;Shi Bingyang
聚酰胺-胺树状大分子（PAMAM）是一种高效的药物载体。然而，固有的细胞毒性和缺乏可检测的信号，以促进跟踪阻碍了它的实际应用。在此，我们开发了一种新的无标记荧光和生物相容性的PAMAM衍生物，通过简单的表面修饰的PAMAM使用乙醛。改性后的PAMAM具有较强的绿色荧光，该荧光是由席夫碱的C=N键通过n−π* 跃迁产生的，同时PAMAM的内在细胞毒性也得到了改善。通过进一步PEG化，荧光PAMAM在人黑素瘤SKMEL 28细胞中表现出优异的细胞内追踪。此外，与原始PAMAM相比，我们的PEG化荧光PAMAM衍生物实现了抗癌药物多柔比星（DOX）的增强的装载和递送效率。重要的是，DOX封装的荧光PAMAM纳米复合物在酸性环境中的加速动力学促进了细胞内药物释放，这表明与游离形式的盐酸阿霉素（DOX·HCl）对黑色素瘤细胞的细胞毒性相当。总的来说，我们的无标记荧光PAMAM衍生物为DOX和其他具有潜在临床重要性的药物提供了可追溯和受控递送的新机会。
Poly(amidoamine) dendrimer (PAMAM) is well-known for its high efficiency as a drug delivery vehicle. However, the intrinsic cytotoxicity and lack of a detectable signal to facilitate tracking have impeded its practical applications. Herein, we have developed a novel label-free fluorescent and biocompatible PAMAM derivative by simple surface modification of PAMAM using acetaldehyde. The modified PAMAM possessed a strong green fluorescence, which was generated by the C=N bonds of the resulting Schiff Bases via n−π* transition, while the intrinsic cytotoxicity of PAMAM was simultaneously ameliorated. Through further PEGylation, the fluorescent PAMAM demonstrated excellent intracellular tracking in human melanoma SKMEL28 cells. In addition, our PEGylated fluorescent PAMAM derivative achieved enhanced loading and delivery efficiency of the anticancer drug doxorubicin (DOX) compared to the original PAMAM. Importantly, the accelerated kinetics of DOX-encapsulated fluorescent PAMAM nanocomposites in an acidic environment facilitated intracellular drug release, which demonstrated comparable cytotoxicity to that of the free-form doxorubicin hydrochloride (DOX·HCl) against melanoma cells. Overall, our label free fluorescent PAMAM derivative offers a new opportunity of traceable and controlled delivery for DOX and other drugs of potential clinical importance.