Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs
Stimuli-Sensitive Dextran Hydrogel Composited with Clickable Reaction-Based Aggregation-Induced Emission Micelles: A Carrier of Hydrophobic Drugs
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DOI：
10.1021/acsapm.3c01603
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发表时间：
2023-09
影响因子：
5
通讯作者：
Linrui Jiang;Wenpeng Li;Qingshan Miao;J. Yang;Shaoyun Shan;Hongying Su
中科院分区：
文献类型：
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作者：
Linrui Jiang;Wenpeng Li;Qingshan Miao;J. Yang;Shaoyun Shan;Hongying Su
在聚合物水凝胶中引入疏水微结构是设计多功能疏水药物载体的一种有效方法。本文提出了将聚集诱导发射(AIE)-活性聚乙烯亚胺（PEI）胶束结合到右旋糖酐水凝胶基质中的荧光胶束-水凝胶复合材料，以改善阿霉素（DOX）的递送。探索了一种基于巯基乙酸锁紧亚胺（MALI）反应的合成方案，以AIEgens（醛功能化四苯基乙烯，TPE-CHO）有效修饰烷基化聚乙烯亚胺（PEI-C12）侧链。通过两亲性tpe - pei - c12的自组装得到具有AIE荧光特性和荧光共振能量转移（FRET）现象的负载dox的胶束纳米颗粒，然后将其封装在含二硫的席夫碱反应形成的葡聚糖水凝胶中。最后，通过体外释放和细胞标记研究，研究了负载DOX的AEI胶束从水凝胶基质中的刺激敏感释放以及随后通过半胶化释放DOX。以上结果表明，AIE胶束-水凝胶体系可以被认为是一种有价值的疏水药物载体，在细胞内成像和药物释放追踪方面具有潜力，特别是在局部给药方面。
Introducing hydrophobic microstructures into polymer hydrogels has been considered recently as an effective strategy to design multifunctional hydrogel-based carriers for hydrophobic drug delivery. Herein, fluorescent micelle–hydrogel composites by combining aggregation-induced emission (AIE)-active polyethylenimine (PEI) micelles into a dextran hydrogel matrix for improving the delivery of doxorubicin (DOX) are presented. A synthetic protocol based on the mercaptoacetic acid locking imine (MALI) reaction was explored to effectively modify the side-chains of alkylated polyethylenimine (PEI-C12) with AIEgens (aldehyde-functionalized tetraphenylethene, TPE-CHO). DOX-loaded micelle nanoparticles with AIE fluorescent properties and fluorescence resonance energy transfer (FRET) phenomenon were obtained via the self-assembly of the resulting amphiphilic TPE-PEI-C12and then encapsulated into dextran hydrogels formed by the disulfide-containing Schiff base reaction. The stimuli-sensitive release of the DOX-loaded AEI micelles from the hydrogel matrix and the following DOX release via demicellization was finally investigated byin vitrorelease and cell-labeling studies. The above results suggest that the AIE micelle–hydrogel system can be considered as a valuable carrier of hydrophobic drugs with potential in intracellular imaging and drug release tracing, especially for local drug delivery.