NDLI: Dual-drug loaded nanoformulation with a galactosamine homing moiety for liver-targeted anticancer therapy

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Guo, Zijian Zhu, Chengcheng Jiao, Yang Zhu, Zhenzhu Muhammad, Nafees Wang, Kun Wang, Xiaoyong
Description	Author Affiliation: Muhammad N ( State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.); Wang X ( State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China. boxwxy@nju.edu.cn.); Wang K ( State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.); Zhu C ( State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.); Zhu Z ( State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.); Jiao Y ( State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.); Guo Z ( State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China. zguo@nju.edu.cn.)
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, $c,c,t-[Pt(NH_{3})_{2}Cl_{2}(O_{2}CC(CH_{3})_{3})_{2}],$ 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.
ISSN	14779226
Issue Number	33
Journal	Dalton Trans.
Volume Number	45
e-ISSN	13645447
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2016-08-16
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Chemistry
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

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