title: Improving anticancer activity and selectivity of camptothecin through conjugation with releasable substance P.
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.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Song
authors.forename: Lingyun
authors.initials: L
authors.lastname: Mu
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Liwei
authors.initials: L
authors.lastname: Liu
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Xing
authors.forename: Kairong
authors.initials: K
authors.lastname: Wang
authors.forename: Zhenya
authors.initials: Z
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms; D018377:Neurotransmitter Agents / Q000737:chemistry; D013373:Substance P / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D018377:Neurotransmitter Agents; D013373:Substance P; D002166:Camptothecin