title: Low-density lipoprotein peptide-combined DNA nanocomplex as an efficient anticancer drug delivery vehicle.
abstract: DNA is a type of potential biomaterials for drug delivery due to its nanoscale geometry, loading capacity of therapeutics, biocompatibility, and biodegradability. Unfortunately, DNA is easily degraded by DNases in the body circulation and has low intracellular uptake. In the present study, we selected three cationic polymers polyethylenimine (PEI), hexadecyl trimethyl ammonium bromide (CTAB), and low-density lipoprotein (LDL) receptor targeted peptide (RLT), to modify DNA and improve the issues. A potent anti-tumor anthracycline-doxorubicin (DOX) was intercalated into DNA non-covalently and the DOX/DNA was then combined with PEI, CTAB, and RLT, respectively. Compact nanocomplexes were formed by electrostatic interaction and could potentially protect DNA from DNases. More importantly, RLT had the potential to enhance intracellular uptake by LDL receptor mediated endocytosis. In a series of in vitro experiments, RLT complexed DNA enhanced intracellular delivery of DOX, increased tumor cell death and intracellular ROS production, and reduced intracellular elimination of DOX. All results suggested that the easily prepared and targeted RLT/DNA nanocomplexes had great potential to be developed into a formulation for doxorubicin with enhanced anti-tumor activity.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.affiliation: Academy of Medical and Pharmaceutical Sciences of Zhengzhou University, Zhengzhou, HeNan 450052, PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Hua
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China.
authors.forename: Pengchao
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001, PR China. Electronic address: zhaoyx@zzu.edu.cn.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D061986:MCF-7 Cells; D058726:Nanoconjugates; D050997:Nanomedicine; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; D002593:Cetrimonium Compounds; D004337:Drug Carriers; C573412:LDLR protein, human; D058726:Nanoconjugates; D010455:Peptides; C000607513:RLT peptide; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D004317:Doxorubicin; D011094:Polyethyleneimine; D004247:DNA; D000077286:Cetrimonium
keywords: Cytotoxicity; DNA nanocomplex; Doxorubicin; Low-density lipoprotein peptide; RLT; Tumor targeting