A Tale of Drug-Carrier Optimization: Controlling Stimuli Sensitivity via Nanoparticle Hydrophobicity through Drug Loading
A Tale of Drug-Carrier Optimization: Controlling Stimuli Sensitivity via Nanoparticle Hydrophobicity through Drug Loading
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DOI：
10.1021/acs.nanolett.0c02319
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发表时间：
2020-09-09
期刊：
影响因子：
10.8
通讯作者：
Wooley, Karen L.
中科院分区：
文献类型：
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作者：
Lin, Yen-Nan;Khan, Sarosh;Wooley, Karen L.
药物分子、纳米载体成分和周围介质之间的相互作用会影响纳米药物的性质和治疗效果。在这项研究中，我们研究了疏水药物的可逆共价负载对纳米粒子内物理性质的影响，并探索了这种有效负载控制策略在调节活性物质的访问权限，从而调节智能纳米材料的刺激敏感性方面的应用。通过改变二硫键连接的喜树碱糖基纳米材料的疏水负载程度来控制谷胱甘肽的敏感性。喜树碱结合度(f(CPT))的增加降低了水的可及性，并减少了谷胱甘肽的释放。尽管f(CPT)最低，但喜树碱的释放速度最快，但其浓度最低。值得注意的是，最高的f(CPT)导致对癌症的选择性比对非癌细胞的选择性提高5.5倍。这项工作展示了控制总有效载荷上的药物负载量及其可用性的重要性，从而代表了药物载体设计的进步。
Interactions between drug molecules, nanocarrier components, and surrounding media influence the properties and therapeutic efficacies of nanomedicines. In this study, we investigate the role that reversible covalent loading of a hydrophobic drug exerts on intra-nanoparticle physical properties and explore the utility of this payload control strategy for tuning the access of active agents and, thereby, the stimuli sensitivity of smart nanomaterials. Glutathione sensitivity was controlled via altering the degree of hydrophobic payload loading of disulfide-linked camptothecin-conjugated sugar-based nanomaterials. Increases in degrees of camptothecin conjugation (f(CPT)) decreased aqueous accessibility and reduced glutathione-triggered release. Although the lowest f(CPT) gave the fastest camptothecin release, it resulted in the lowest camptothecin concentration. Remarkably, the highest f(CPT) resulted in a 5.5-fold improved selectivity against cancer vs noncancerous cells. This work represents an advancement in drug carrier design by demonstrating the importance of controlling the amount of drug loading on the overall payload and its availability.