Chlorambucil gemcitabine conjugate nanomedicine for cancer therapy.
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.
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.
Mingliang
M
Fan
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.
Xiaofei
X
Liang
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.
Zonghai
Z
Li
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.
Hongyang
H
Wang
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.
Danbo
D
Yang
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.
Bizhi
B
Shi
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002699:Chlorambucil / Q000008:administration & dosage* / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000008:administration & dosage / Q000627:therapeutic use*; D050997:Nanomedicine / Q000379:methods; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D058726:Nanoconjugates; D003841:Deoxycytidine; D002699:Chlorambucil; D000093542:Gemcitabine
Chlorambucil; Conjugate; Gemcitabine; Nanodrug; Nanoparticle