title: Cyclic RGDfK Peptide Functionalized Polymeric Nanocarriers for Targeting Gemcitabine to Ovarian Cancer Cells.
abstract: Current cancer chemotherapies commonly suffer from nonspecificity, drug resistance, poor bioavailability, and narrow therapeutic indices. To achieve the optimum drug efficacy, we designed a polymeric drug delivery system for targeted intracellular delivery of a clinically approved, water-soluble anticancer drug, gemcitabine hydrochloride (GEM). We utilized the unique ability of a cyclic pentapeptide cRGDfK to specifically target αvβ3 integrin receptors that are overexpressed on SKOV-3 human ovarian cancer cells. This significantly increased the effective intracellular drug concentration even at low doses, thereby remarkably improving the chemotherapeutic potential of GEM. cRGDfK-conjugated, GEM-loaded nanoparticles reduced the nonspecific hemolytic cytotoxicity of the drug, simultaneously influencing intracellular processes such as mitochondrial membrane potential (DΨm), reactive oxygen species (ROS) levels, and apoptosis, thereby favorably influencing drug antiproliferative efficacy.
authors.affiliation: Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University , Melbourne, VIC 3001, Australia.|Health Innovations Research Institute, RMIT University , Melbourne, VIC 3083, Australia.|IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.|Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Kulhari
authors.affiliation: Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University , Melbourne, VIC 3001, Australia.|Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.
authors.forename: Deep
authors.initials: D
authors.lastname: Pooja
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.
authors.forename: Raju
authors.initials: R
authors.lastname: Kota
authors.affiliation: Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University , Melbourne, VIC 3001, Australia.|Health Innovations Research Institute, RMIT University , Melbourne, VIC 3083, Australia.|IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.|Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.
authors.forename: T Srinivasa
authors.initials: TS
authors.lastname: Reddy
authors.affiliation: School of Chemistry, Monash University , Clayton, VIC 3800, Australia.
authors.forename: Rico F
authors.initials: RF
authors.lastname: Tabor
authors.affiliation: Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University , Melbourne, VIC 3001, Australia.|Health Innovations Research Institute, RMIT University , Melbourne, VIC 3083, Australia.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shukla
authors.affiliation: Health Innovations Research Institute, RMIT University , Melbourne, VIC 3083, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
authors.affiliation: Medicinal Chemistry & Pharmacology Division, CSIR-Indian Institute of Chemical Technology , Hyderabad, Telangana 500007, India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
authors.affiliation: Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University , Melbourne, VIC 3001, Australia.|Health Innovations Research Institute, RMIT University , Melbourne, VIC 3083, Australia.
authors.forename: Vipul
authors.initials: V
authors.lastname: Bansal
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010456:Peptides, Cyclic / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010455:Peptides; D010456:Peptides, Cyclic; D011108:Polymers; D017382:Reactive Oxygen Species; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: cRGDfK; gemcitabine; integrin; ovarian cancer; targeted drug delivery