Citation: Chen Can, Li Yiyan, Yu Xiaoping, Jiang Qinglin, Xu Xiaohong, Yang Qian, Qian Zhiyong. Bone-targeting melphalan prodrug with tumor-microenvironment sensitivity: Synthesis, in vitro and in vivo evaluation[J]. Chinese Chemical Letters, ;2018, 29(11): 1609-1612. doi: 10.1016/j.cclet.2018.02.010 shu

Bone-targeting melphalan prodrug with tumor-microenvironment sensitivity: Synthesis, in vitro and in vivo evaluation

Chen Can ^a ,
Li Yiyan ^b ,
Yu Xiaoping ^c ,
Jiang Qinglin ^b ,
Xu Xiaohong ^b,, ,
Yang Qian ^b,, ,
Qian Zhiyong ^d

a.
The First Affiliated Hospital, Chengdu Medical College, Chengdu 610500, China
b.
The School of Pharmacy, College Key Laboratory of Sichuan Province for Specific Structure of Small Molecule Drugs, Chengdu Medical College, Chengdu 610500, China
c.
The Public Health Department, Chengdu Medical College, Chengdu 610500, China
d.
State Key Laboratory and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

Corresponding author: Xu Xiaohong, xoxoho@163.com Yang Qian, yoyoyoung8293@gmail.com
Received Date: 29 November 2017
Revised Date: 4 February 2018
Accepted Date: 23 February 2018
Available Online: 2 November 2018

Figures(5)

Bone tumor is a refractory neoplastic growth of tissue in bone. According to the unique environment and phys-chemical characteristics of bone tissues, the chemotherapeutic agents are unlikely to prolong the survival of patients and often associated with systemic side effects. The bone targeting drug delivery via systemic administration may provide both better treatment efficacy and less frequent administration. In this study, we describe the synthesis, in vitro and in vivo evaluation of novel melphalan-bisphosphonate hybrids, with a tumor microenvironment sensitive linkage, which could be enzymatic activation under tumor microenvironment conditions. We have also evaluated the in vitro targeting efficiency of these prodrugs via the affinity of hydroxyapatite (HA) and cellular proliferation. The in vivo distribution suggested the bisphosphonate conjugated prodrugs with high bone selectivity.
- Bone targeted,
- Bisphosphonates,
- Melphalan,
- Tumor-microenvironment sensitive,
- Prodrug
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