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.
Copyright © 2015 Elsevier B.V. All rights reserved.
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