title: Binding and uptake of novel RGD micelles to the αvβ3 integrin receptor for targeted drug delivery.
abstract: OBJECTIVE
  To understand the binding and internalization of novel RGD micelles in tumor cells that overexpress the αvβ3 integrin receptor.
  
  
  METHODS
  Peptide amphiphiles containing a C16 or C18 fatty-acid chain with one or two ADA units linked to an RGD motif were prepared, characterized, and assessed for their binding specificity to the αvβ3 receptor. The internalization of the amphiphiles was evaluated by confocal microscopy and cytotoxicity studies in A2058 cells that overexpress the αvβ3 integrin receptor.
  
  
  RESULTS
  The CMC and size and of RGD micelles ranged from 9 to 30 μM and 130 to 300 nm, respectively. Micelles showed good in vitro stability by retaining their micellar integrity and good specificity by binding to the αvβ3 integrin receptor in an RGD-dependent manner. Confocal studies showed higher intracellular fluorescence when FITC was delivered through the micelles compared with its free form and showed significantly higher FITC uptake at 37 °C versus 4 °C (p < 0.05). The lower IC50 values were obtained when paclitaxel was delivered to A2058 cells via the RGD-loaded carriers (3.6-4.87 nM) compared with unencapsulated drug (7.86 nM), further demonstrated micelle specificity to the αvβ3 receptor.
  
  
  CONCLUSIONS
  RGD micelles bound specifically to the αvβ3 receptor and their uptake was mediated by an endocytic process.
authors.affiliation: Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific , Stockton, CA , USA and.
authors.forename: April
authors.initials: A
authors.lastname: Raj
authors.forename: Poonam
authors.initials: P
authors.lastname: Saraf
authors.forename: Narashima Murthy
authors.initials: NM
authors.lastname: Javali
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Bhaskara
authors.initials: B
authors.lastname: Jasti
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005454:Fluorescence Polarization; D031541:Fluorescence Resonance Energy Transfer; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008823:Micelles; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage; D011485:Protein Binding
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D039302:Integrin alphaVbeta3; D008823:Micelles; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel
keywords: Confocal microscopy; RGD peptide amphiphile; cytotoxicity; fluorescence polarization; micelle stability; receptor-mediated endocytosis