Wang Huan, Liu Xinchen, Yan Xiangyu, Du Yong, Pu Fang, Ren Jinsong, Qu Xiaogang
State Key Laboratory of Rare Earth Resources Utilization and Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences Changchun Jilin 130022 P. R. China
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University Changchun Jilin 130021 P. R. China.
Chem Sci. 2024 Sep 3;15(39):16156-68. doi: 10.1039/d4sc05280c.
The drug design principles are of great value in developing nanomedicines with favorable functionalities. Herein we propose a nanocarbon-enabled hybridization strategy to construct a pharmacologically cooperative nanodrug for improved cancer therapy in the light of pharmacophore hybridization in medicinal chemistry and the synthetic principles of nanocarbons. An antioxidant defense pharmacological inhibitor and a co-nucleation precursor are structurally hybridized into nanodrugs (SCACDs) forming carbon quantum dots. These SCACDs elicit dual enhanced bioactivities, including superior sonocatalytic activity that arose from the appropriate band structure of the pharmacophoric carbon cores, and more than an order of magnitude higher antioxidant defense inhibitory activity than the pharmacological inhibitor conveying the bioactive pharmacophores from the molecular level to nanoscale. , SCACDs possess a long body retention and desirable biodistribution to eliminate melanoma cells at a very low injection dose. The present study provides a viable yet effective strategy for the development of pharmacologically cooperative nanodrugs to achieve remarkably improved therapeutic efficacy.
药物设计原则在开发具有良好功能的纳米药物方面具有重要价值。在此，我们根据药物化学中的药效团杂交和纳米碳的合成原理，提出了一种基于纳米碳的杂交策略，以构建一种具有药理协同作用的纳米药物，用于改善癌症治疗。一种抗氧化防御药理抑制剂和一种共成核前体在结构上杂交成纳米药物（SCACD），形成碳量子点。这些SCACD具有双重增强的生物活性，包括由于药效团碳核的适当能带结构而产生的优异声催化活性，以及比药理抑制剂高一个数量级以上的抗氧化防御抑制活性，将生物活性药效团从分子水平传递到纳米尺度。此外，SCACD具有长时间的体内滞留和理想的生物分布，能够以非常低的注射剂量消除黑色素瘤细胞。本研究为开发具有药理协同作用的纳米药物以实现显著提高的治疗效果提供了一种可行而有效的策略。
