1. Improving anticancer activity and selectivity of camptothecin through conjugation with releasable substance P
- Author
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Liwei Liu, Kairong Wang, Jingjing Song, Wei Zhang, Rui Wang, Yanhong Xing, Lingyun Mu, Bangzhi Zhang, and Zhen-Ya Li
- Subjects
Cell Survival ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Substance P ,Biochemistry ,chemistry.chemical_compound ,Drug Delivery Systems ,Cell Line, Tumor ,Neoplasms ,Drug Discovery ,Tachykinin receptor 1 ,medicine ,Humans ,heterocyclic compounds ,Cytotoxicity ,neoplasms ,Molecular Biology ,Neurotransmitter Agents ,Molecular Structure ,biology ,Chemistry ,Topoisomerase ,Organic Chemistry ,Biological activity ,Enzyme inhibitor ,Delayed-Action Preparations ,biology.protein ,Molecular Medicine ,Camptothecin ,Linker ,medicine.drug - Abstract
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.
- Published
- 2011