title: Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles.
abstract: Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or intrinsic and acquired resistance limits its application in many types of cancer. CXCR4 is a chemokine receptor which implicates in metastasis of cancers including lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear type of low molecular weight CXCR4 antagonist. In this study, we investigated the possibility of using LFC131 conjugated nanoparticles for targeted delivering doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was conjugated to sodium carboxylmethyl cellulose coated poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar basal epithelial cells called A549 cells were higher and faster than that of untargeted nanoparticles. The specificity of CXCR4-mediated internalization of LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4 monoclonal antibody. Cell studies suggested that sustained release of doxorubicin afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and controlled release drug delivery system.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Srinakharinwirot University, Nakhonnayok, Thailand. Electronic address: chuda@g.swu.ac.th.
authors.forename: Chuda
authors.initials: C
authors.lastname: Chittasupho
authors.affiliation: Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand.
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Lirdprapamongkol
authors.affiliation: Thailand Institute of Nuclear Technology, Nakhonnayok, Thailand.
authors.forename: Prartana
authors.initials: P
authors.lastname: Kewsuwan
authors.affiliation: Faculty of Pharmacy, Thammasat University, Pathum Thani, Thailand.
authors.forename: Narong
authors.initials: N
authors.lastname: Sarisuta
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
chemical_list: D000903:Antibiotics, Antineoplastic; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin
keywords: A549 cells; CXCR4; CXCR4 antagonist; Doxorubicin; Lung cancer; Targeted drug delivery