title: Surface-engineered dendrimers for dual drug delivery: a receptor up-regulation and enhanced cancer targeting strategy.
abstract: The present study is aimed at developing and evaluating a combined strategy of dual drug delivery, receptor up-regulation, and drug targeting. The dendritic architectures were synthesized and characterized by IR, (1)H-NMR, and (13)C-NMR spectroscopy. The pH-responsive simultaneous release behavior of the loaded bioactive from the carrier was also explored. The cell line studies for MTT cytotoxicity, receptor blockade, and receptor up-regulation assays were performed on HeLa cells. Treatment of cells with low concentration of all-trans retinoic acid (ATRA, approximately 1 microM) caused a selective up-regulation of folate receptors by 2.21-folds when compared with that of untreated control, after 48 h. ATRA showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC(50) value of naked methotrexate (MTX)-ATRA combination and dendrimer-loaded MTX-ATRA combination were found to be approximately 0.1 and 10 microM, respectively, while folate-anchored dendrimer loaded with MTX-ATRA showed a selectively lowered IC(50) value of 0.04 microM. It was concluded that in allied ailments like cancer, the proposed dual-drug delivery modality bearing anti-cancer bioactive in conjunction with folate receptor up-regulating cargo may prove to be a promising approach toward the development of a flourishing cancer therapy.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Tekade
authors.forename: Tathagata
authors.initials: T
authors.lastname: Dutta
authors.forename: Abhishek
authors.initials: A
authors.lastname: Tyagi
authors.forename: Alok Chandra
authors.initials: AC
authors.lastname: Bharti
authors.forename: Bhudev Chandra
authors.initials: BC
authors.lastname: Das
authors.forename: Narendra Kumar
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D058973:Folate Receptors, GPI-Anchored; D006367:HeLa Cells; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000008:administration & dosage* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D050091:Dendrimers; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D014212:Tretinoin; D008727:Methotrexate