Modular design of cyclic peptide - polymer conjugate nanotubes for delivery and tunable release of anti-cancer drug compounds
Modular design of cyclic peptide - polymer conjugate nanotubes for delivery and tunable release of anti-cancer drug compounds
复制标题
用于抗癌药物化合物的递送和可调释放的环肽-聚合物缀合物纳米管的模块化设计
DOI：
10.1016/j.jconrel.2024.01.023
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发表时间：
2024
影响因子：
10.8
通讯作者：
Hill S
中科院分区：
文献类型：
--
作者：
Hill S
由于高纵横比纳米材料具有很强的细胞关联性和较长的体内循环时间，因此最近成为有前途的药物递送载体。环肽-聚合物共轭纳米管由于其细长的形态、超分子组成和高度的柔韧性而成为极好的候选材料，因为它们在操纵氨基酸序列和聚合物类型方面具有通用性。在这项工作中，我们探索了一种纳米管结构的使用，在这种纳米管结构上，一种有效的抗癌药物喜树碱附着在亲水或两亲性RAFT聚合物上，从而保护货物。我们表明，对可切割连接体类型和聚合物结构的细微修改对生物条件下药物释放速度有显着影响。体外研究显示，2D和3D模型中的多种癌细胞系对纳米管治疗有有效反应，类似的荧光标记材料揭示了有关细胞摄取程度和细胞内命运的关键机制信息。重要的是，指示特定药物释放谱的能力表明这些纳米材料作为载体的潜力，可以提供持续的药物浓度以获得最大的治疗效果。
High aspect-ratio nanomaterials have recently emerged as promising drug delivery vehicles due to evidence of strong cellular association and prolonged in vivo circulation times. Cyclic peptide - polymer conjugate nanotubes are excellent candidates due to their elongated morphology, their supramolecular composition and high degree of pliability due to the versatility in manipulating amino acid sequence and polymer type. In this work, we explore the use of a nanotube structure on which a potent anti-cancer drug, camptothecin, is attached alongside hydrophilic or amphiphilic RAFT polymers, which shield the cargo. We show that subtle modifications to the cleavable linker type and polymer architecture have a dramatic influence over the rate of drug release in biological conditions.In vitrostudies revealed that multiple cancer cell lines in 2D and 3D models responded effectively to the nanotube treatment, and analogous fluorescently labelled materials revealed key mechanistic information regarding the degree of cellular uptake and intracellular fate. Importantly, the ability to instruct specific drug release profiles indicates a potential for these nanomaterials as vectors which can provide sustained drug concentrations for a maximal therapeutic effect.