Chlorambucil gemcitabine conjugate nanomedicine for cancer therapy

Mingliang Fan; Xiaofei Liang; Zonghai Li; Hongyang Wang; Danbo Yang; Bizhi Shi

doi:10.1016/j.ejps.2015.08.013

Chlorambucil gemcitabine conjugate nanomedicine for cancer therapy

Eur J Pharm Sci. 2015 Nov 15:79:20-6. doi: 10.1016/j.ejps.2015.08.013. Epub 2015 Sep 2.

Authors

Mingliang Fan¹, Xiaofei Liang¹, Zonghai Li¹, Hongyang Wang¹, Danbo Yang², Bizhi Shi³

Affiliations

¹ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China. Electronic address: danboyang@126.com.
³ State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25/Ln2200, XieTu Rd, Shanghai 200032, China. Electronic address: shibizhi@126.com.

PMID: 26342774
DOI: 10.1016/j.ejps.2015.08.013

Abstract

Self-assembly of anticancer small molecules into nanostructures may represent an attractive approach to improve the treatment of experimental solid tumors. As a proof of concept, we designed and synthesized the conjugate prodrug of hydrophilic gemcitabine by its covalent coupling to hydrophobic chlorambucil via a hydrolyzable ester linkage. The resulting amphiphilic conjugates self-assembled into nanoparticles in water and exhibited significant anticancer activity in vitro against a variety of human cancer cells. In vivo anticancer activity of these nanoparticles has been tested on subcutaneous grafted SMMC-7721 hepatocellular carcinoma model. Such chlorambucil gemcitabine conjugate nanomedicine should have potential applications in cancer therapy.

Keywords: Chlorambucil; Conjugate; Gemcitabine; Nanodrug; Nanoparticle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimetabolites, Antineoplastic / administration & dosage*
Antimetabolites, Antineoplastic / therapeutic use
Antineoplastic Agents, Alkylating / administration & dosage*
Antineoplastic Agents, Alkylating / therapeutic use
Apoptosis / drug effects
Carcinoma, Hepatocellular / drug therapy
Cell Cycle / drug effects
Cell Line, Tumor / drug effects
Chlorambucil / administration & dosage*
Chlorambucil / therapeutic use
Deoxycytidine / administration & dosage
Deoxycytidine / analogs & derivatives*
Deoxycytidine / therapeutic use
Female
Gemcitabine
Humans
Liver Neoplasms / drug therapy
Mice
Mice, Inbred BALB C
Nanoconjugates / administration & dosage
Nanoconjugates / therapeutic use*
Nanomedicine / methods
Neoplasm Transplantation
Neoplasms / drug therapy*

Substances

Antimetabolites, Antineoplastic
Antineoplastic Agents, Alkylating
Nanoconjugates
Deoxycytidine
Chlorambucil
Gemcitabine