title: iRGD decorated lipid-polymer hybrid nanoparticles for targeted co-delivery of doxorubicin and sorafenib to enhance anti-hepatocellular carcinoma efficacy.
abstract: The combination of doxorubicin (DOX) with sorafenib (SOR) has proven an effective strategy to enhance anti-hepatocellular carcinoma (HCC) efficacy. However, respective in vivo pharmacokinetic profiles and different endocytosis capacities of these two drugs greatly hinder their current application. Herein, the tumor-targeting peptide iRGD decorated lipid-polymer hybrid nanoparticles (NPs) with a shell-core structure were developed for co-delivery of DOX and SOR (DOX+SOR/iRGD NPs). After the drug ratio was optimized, the stabilized DOX+SOR/iRGD NPs were prepared. Through the iRGD-integrin recognition, DOX+SOR/iRGD NPs showed synergistic cytotoxicity, pro-apoptotic ability and enhanced internalization rate in human liver cancer HepG2 cells. In vivo pharmacokinetic result demonstrated that an extended circulation and bioavailability of DOX+SOR/iRGD NPs than free drugs. More importantly, DOX+SOR/iRGD NPs significantly enhanced antitumor efficiency in HCC xenograft mouse models. Overall, this study describes a promising nanoparticulate drug co-delivery strategy to combine clinical anticancer drugs and enhance anti-HCC efficacy.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Biomedical Engineering, Columbia University, NY, USA.
authors.forename: Hon Fai
authors.initials: HF
authors.lastname: Chan
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Melissa
authors.initials: M
authors.lastname: Skibba
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: cuiliang1234@163.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China. Electronic address: mwchen@umac.mo.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D053758:Nanoparticles; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011108:Polymers; D000077157:Sorafenib
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008055:Lipids; D010671:Phenylurea Compounds; D011108:Polymers; D009536:Niacinamide; D004317:Doxorubicin; D000077157:Sorafenib
keywords: Active targeting; Doxorubicin; Hepatocellular carcinoma; Sorafenib; iRGD peptide