title: Dual-drug loaded nanoformulation with a galactosamine homing moiety for liver-targeted anticancer therapy.
abstract: Drug resistance and unfavorable pharmacokinetics are the major obstacles for conventional anticancer drugs. A combination of different anticancer drugs into one formulation is a common strategy to alleviate the side effects of individual drugs in clinical practice. Platinum anticancer drugs are the typical defective therapeutic agents for cancer chemotherapy and have poor selectivity for tumor cells. In this study, a nanosystem composed of poly(lactic-co-glycolic acid) (PLGA), Pt(IV) prodrug (PPD) and α-tocopheryl succinate (α-TOS) was designed to overcome these defects. The Pt(IV) prodrug, c,c,t-[Pt(NH3)2Cl2(O2CC(CH3)3)2], was prepared by the reaction of oxoplatin with trimethylacetic anhydride and its structure was characterized by X-ray crystallography. The PPD and α-TOS self-assembled with PLGA, forming a dual-drug loaded nanoparticle (DDNP). The surface of the DDNP was decorated with galactosamine (G), giving rise to a G-DDNP that can actively target the liver cancer cells through the overexpressed asialoglycoprotein receptors. The DDNPs and G-DDNPs were characterized by SEM, TEM, and DLS. They are spherical in shape with required polydispersity and suitable mean size (ca. 150 nm). The in vitro cytotoxicity of DDNPs and G-DDNPs was tested against the human SMMC-7721 liver cancer cell line. G-DDNPs are more potent than the corresponding free drugs and untargeted DDNP, showing that some synergistic and tumor-specific effects are achieved by this strategy. The results demonstrate that dual-drug loaded nanoformulations with tumor-targeting function could be effective anticancer agents for conquering the shortcomings related to single-drug chemotherapy.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.
authors.forename: Nafees
authors.initials: N
authors.lastname: Muhammad
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China. boxwxy@nju.edu.cn.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.
authors.forename: Zhenzhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D065546:Drug Liberation; D005688:Galactosamine / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D008113:Liver Neoplasms; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010984:Platinum / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011355:Prodrugs; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010984:Platinum; D005688:Galactosamine; D053148:Caspase 3; D024502:alpha-Tocopherol