title: Hierarchical targeted hepatocyte mitochondrial multifunctional chitosan nanoparticles for anticancer drug delivery.
abstract: The overwhelming majority of drugs exert their pharmacological effects after reaching their target sites of action, however, these target sites are mainly located in the cytosol or intracellular organelles. Consequently, delivering drugs to the specific organelle is the key to achieve maximum therapeutic effects and minimum side-effects. In the work reported here, we designed, synthesized, and evaluated a novel mitochondrial-targeted multifunctional nanoparticles (MNPs) based on chitosan derivatives according to the physiological environment of the tumor and the requirement of mitochondrial targeting drug delivery. The intelligent chitosan nanoparticles possess various functions such as stealth, hepatocyte targeting, multistage pH-response, lysosomal escape and mitochondrial targeting, which lead to targeted drug release after the progressively shedding of functional groups, thus realize the efficient intracellular delivery and mitochondrial localization, inhibit the growth of tumor, elevate the antitumor efficacy, and reduce the toxicity of anticancer drugs. It provides a safe and efficient nanocarrier platform for mitochondria targeting anticancer drug delivery.
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China; State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, PR China. Electronic address: czpcpu2000@hotmail.com.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Henan University, Kaifeng 475001, PR China.
authors.forename: Liujie
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hospital Pharmacy, The 302nd Hospital of PLA, Beijing 100039, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Jiayu
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines (China Pharmaceutical University), Nanjing 210009, PR China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Pharmacy, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Traditional Chinese Medicine, Nanjing 210046, PR China. Electronic address: liweidong0801@163.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis; D048271:Chitosan / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D012545:Schiff Bases; D013331:Strychnine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D012545:Schiff Bases; C083806:brucine; D048271:Chitosan; D013331:Strychnine
keywords: Cancer therapy; Drug delivery; Hierarchical; Mitochondrial-targeted; Multifunctional nanoparticles; pH-response