Department of Biomedical Sciences, Faculty of Medicine & Health Sciences , Macquarie University , Sydney , New South Wales 2109 , Australia.
Queensland Brain Institute , The University of Queensland , Saint Lucia , Queensland 4072 , Australia.
Biomacromolecules. 2019 May 13;20(5):2148-2158. doi: 10.1021/acs.biomac.9b00494. Epub 2019 Apr 24.
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.
聚酰胺-胺树枝状聚合物（PAMAM）作为药物递送载体以其高效性而闻名。然而，其内在的细胞毒性和缺乏可检测的信号来促进追踪，限制了其实际应用。在此，我们通过用乙醛简单地对 PAMAM 进行表面修饰，开发了一种新型的无标记荧光和生物相容的 PAMAM 衍生物。修饰后的 PAMAM 具有很强的绿色荧光，这是通过生成的席夫碱的 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。通过进一步的 PEG 化，荧光 PAMAM 在人黑色素瘤 SKMEL28 细胞中表现出出色的细胞内追踪能力。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阿霉素（DOX）的载药量和递送效率的提高。重要的是，在酸性环境中，包载 DOX 的荧光 PAMAM 纳米复合材料的加速动力学促进了细胞内药物释放，其对黑色素瘤细胞的细胞毒性与游离形式的盐酸阿霉素（DOX·HCl）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一种新的可追踪和控制递药的机会。
