Gemcitabine-based polymer-drug conjugate for enhanced anticancer effect in colon cancer
作者
Liang, TJ;Zhou, ZM;Cao, YQ;Ma, MZ;Wang, XJ;Jing, K
作者单位
[Liang, Tie-Jun; Ma, Ming-Ze; Wang, Xiao-Jun] Shandong Univ, Dept Digest Dis, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China.;-;[Zhou, Zhong-Mei] Taian City Cent Hosp, Dept Neonatol, Tai An 271000, Shandong, Peoples R China.;-;[Cao, Ying-Qing] Taian City Cent Hosp, Dept Anus & Intestine Surg, 29 Longan Rd, Tai An 271000, Shandong, Peoples R China.;-;[Jing, Kai] Huaiyin Peoples Hosp, Dept Gastrointestinal Surg, Jinan 250021, Shandong, Peoples R China.
摘要
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 (similar to 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. (C) 2016 Elsevier B.V. All rights reserved.
关键词
COMPLEX MICELLES; DELIVERY; DOXORUBICIN; PHARMACOKINETICS; CHEMOTHERAPY; THERAPY
基本信息
