Departments of Chemistry, Chemical Engineering, and Materials Science & Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, College Station, Texas 77842, United States.
College of Medicine, Texas A&M University, Bryan, Texas 77807, United States.
Nano Lett. 2020 Sep 9;20(9):6563-6571. doi: 10.1021/acs.nanolett.0c02319. Epub 2020 Aug 10.
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 () decreased aqueous accessibility and reduced glutathione-triggered release. Although the lowest gave the fastest camptothecin release, it resulted in the lowest camptothecin concentration. Remarkably, the highest 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.
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，我们研究了疏水性药物的可逆共价加载对纳米颗粒内部物理性质的影响，并探讨了这种载药控制策略在调节活性物质的进入以及由此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缀合糖基纳米材料的疏水性载药负载程度来控制谷胱甘肽的敏感性。喜树碱的连接程度增加（）会降低水相的可及性，并减少谷胱甘肽触发的释放。虽然最低的 （）给出了最快的喜树碱释放，但它导致了最低的喜树碱浓度。值得注意的是，最高的 （）导致对癌细胞与非癌细胞的选择性提高了 5.5 倍。这项工作通过证明控制药物载药量对整体载药量及其可及性的重要性，代表了药物载体设计的一项进展。
