Gemcitabine-based polymer-drug conjugate for enhanced anticancer effect in colon cancer.
In this study, we have demonstrated gemcitabine (GEM)-conjugated amphiphilic biodegradable polymeric drug carriers. Our aim was to increase the chemotherapeutic potential of GEM in colon cancer by forming a unique polymer-drug conjugates. The polymer-drug conjugate micelles were nanosized with a typical spherical shape. The GEM-conjugated methoxy poly(ethylene glycol)-poly(lactic acid) (GEM-PL) exhibited a controlled release of drug in both the pH conditions. The developed GEM-PL efficiently killed the HT29 cancers cells in a typical time dependent manner. The clonogenic assay further confirmed the superior anticancer effect of GEM-PL which showed least number of colonies. GEM-PL formulation exhibited a significantly higher apoptosis of cancer cells (∼25%) when stained using Annexin-V/PI kit. Conjugation of GEM to the mPEG-PLA significantly enhanced the blood circulation potential in animal model compared to that of free GEM. GEM-PL could prevent quick elimination of the drug and can provide sufficient time for the greater accumulation of GEM at the tumor sites. GEM-PL showed a remarkable tumor regression effect as evident from the lowest tumor volume in HT-29 containing tumor model. Overall, mPEG-PLA/GEM conjugates showed the potential of polymer-based drug targeting and might hold significant clinical potential in the treatment of colon cancers.
Department of Digestive Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Tie-Jun
TJ
Liang
Department of Neonatology, Taian City Central Hospital, Taian, 271000 Shandong, China.
Zhong-Mei
ZM
Zhou
Department of Anus & Intestine Surgery, Taian City Central Hospital, Taian, 271000 Shandong, China. Electronic address: baoyingqing@hotmail.com.
Ying-Qing
YQ
Cao
Department of Digestive Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Ming-Ze
MZ
Ma
Department of Digestive Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
Xiao-Jun
XJ
Wang
Department of Gastrointestinal Surgery, Huaiyin People's Hospital, Jinan, Shandong 250021, China.
Kai
K
Jing
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D065546:Drug Liberation; D019073:HT29 Cells; D006801:Humans; D008819:Mice, Nude; D008823:Micelles; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D047368:Tumor Burden / Q000187:drug effects; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D003841:Deoxycytidine; D011092:Polyethylene Glycols; D000093542:Gemcitabine
Anticancer efficacy; Apoptosis; Gemcitabine; Polylactide; Polymer-drug conjugates