Can Wang1, Liang Su2, Chengsheng Wu3, Jianlin Wu4, Chengbao Zhu5, Guangying Yuan5. 1. a Department of Hepatology , Jinan Infectious Disease Hospital , Ji'nan , Shandong , 250021 , P.R. China ; 2. b Department of Infectious Disease , Jinan Infectious Disease Hospital , Ji'nan , Shandong , 250021 , P.R. China ; 3. c Department of Hepatology , Taian TCM Hospital , Taian , Shandong , 271000 , P.R. China ; 4. d Basic Medical College of Shandong University of Traditional Chinese Medicine , Ji'nan , Shandong , 250355 , P.R. China ; 5. e Department of Clinical Laboratory , Jinan Infectious Disease Hospital , Ji'nan , Shandong , 250021 , P.R. China.
Abstract
CONTEXT: Combination therapies provide a potential solution to address the tumor heterogeneity and drug resistance issues by taking advantage of distinct mechanisms of action of the multiple therapeutics. OBJECTIVE: To design arginine-glycineaspartic acid (RGD) modified lipid-coated nanoparticles (NPs) for the co-delivery of the hydrophobic drugs against hepatocellular carcinoma (HCC). MATERIALS AND METHODS: RGD modified lipid-coated PLGA NPs were developed for the targeted delivery of both sorafenib (SRF) and quercetin (QT) (RGD-SRF-QT NPs). Chemical-physical characteristics and release profiles were evaluated. In vitro cell viability assays were carried out on HCC cells. In vivo antitumor efficacies were evaluated in HCC animal model. RESULTS AND DISCUSSION: The combination of SRF and QT formulations was more effective than the single drug formulations in both NPs and solution groups. RGD-SRF-QT NPs achieved the most significant tumor growth inhibition effect in vitro and in vivo. CONCLUSION: The resulting NPs could provide a promising platform for co-delivery of multiple anticancer drugs for achievement of combinational therapy and could offer potential for enhancing the therapeutic efficacy on HCC.
CONTEXT: Combination therapies provide a potential solution to address the tumor heterogeneity and drug resistance issues by taking advantage of distinct mechanisms of action of the multiple therapeutics. OBJECTIVE: To design arginine-glycineaspartic acid (RGD) modified lipid-coated nanoparticles (NPs) for the co-delivery of the hydrophobic drugs against hepatocellular carcinoma (HCC). MATERIALS AND METHODS: RGD modified lipid-coated PLGA NPs were developed for the targeted delivery of both sorafenib (SRF) and quercetin (QT) (RGD-SRF-QT NPs). Chemical-physical characteristics and release profiles were evaluated. In vitro cell viability assays were carried out on HCC cells. In vivo antitumor efficacies were evaluated in HCC animal model. RESULTS AND DISCUSSION: The combination of SRF and QT formulations was more effective than the single drug formulations in both NPs and solution groups. RGD-SRF-QT NPs achieved the most significant tumor growth inhibition effect in vitro and in vivo. CONCLUSION: The resulting NPs could provide a promising platform for co-delivery of multiple anticancer drugs for achievement of combinational therapy and could offer potential for enhancing the therapeutic efficacy on HCC.
Authors: Thangirala Sudha; Dhruba J Bharali; Murat Yalcin; Noureldien He Darwish; Melis Debreli Coskun; Kelly A Keating; Hung-Yun Lin; Paul J Davis; Shaker A Mousa Journal: Int J Nanomedicine Date: 2017-02-15