Improving anticancer activity and selectivity of camptothecin through conjugation with releasable substance P.
Improving anticancer activity and selectivity of camptothecin through conjugation with releasable substance P.
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DOI：
10.1016/j.bmcl.2011.01.013
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发表时间：
2011-03
影响因子：
2.7
通讯作者：
Wei Zhang-;Jingjing Song;L. Mu;Bang-zhi Zhang;Liwei Liu;Yanhong Xing;Kairong Wang;Zhenya Li;Rui Wang
中科院分区：
文献类型：
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作者：
Wei Zhang-;Jingjing Song;L. Mu;Bang-zhi Zhang;Liwei Liu;Yanhong Xing;Kairong Wang;Zhenya Li;Rui Wang
P 物质是一种 11 个残基的神经肽，可以通过与神经激肽-1 受体的特异性相互作用而快速内化。因此，我们通过可释放的二硫键碳酸酯连接体设计并合成了P物质靶向喜树碱（CPT）缀合物。所有缀合物对高度过表达神经激肽-1受体的癌细胞表现出与游离CPT相当或更强的细胞毒性。更重要的是，与CPT相比，缀合物的选择性显着提高。我们的结果表明这些缀合物可能成为新化疗药物的有希望的候选者。此外，增加CPT负载或CPT与P物质C端六肽的附着是增强P物质靶向缀合物的治疗功效的有用策略。
Substance P, an 11-residue neuropeptide, can be rapidly internalized through specific interaction with the neurokinin-1 receptor. Therefore, we designed and synthesized the substance P targeted camptothecin (CPT) conjugates via a releasable disulfide carbonate linker. All the conjugates exhibited comparable or stronger cytotoxicity to cancer cells that highly over-express neurokinin-1 receptor than free CPT. More importantly, the selectivity of conjugates was significantly improved compared with CPT. Our results indicated that these conjugates can be promising candidates for new chemotherapeutic drugs. In addition, increasing CPT loading or attachment of CPT to the C-terminal hexapeptide of substance P are useful strategies to enhance the therapeutic efficacy of substance P targeted conjugates.