Binding and uptake of novel RGD micelles to the αvβ3 integrin receptor for targeted drug delivery.
PURPOSE
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.


CONCLUSION
RGD micelles bound specifically to the αvβ3 receptor and their uptake was mediated by an endocytic process.
['Raj|April|A|', 'Saraf|Poonam|P|', 'Javali|Narashima Murthy|NM|', 'Li|Xiaoling|X|', 'Jasti|Bhaskara|B|']
D000972:Antineoplastic Agents, Phytogenic D016503:Drug Delivery Systems D005454:Fluorescence Polarization D031541:Fluorescence Resonance Energy Transfer D039302:Integrin alphaVbeta3 D008823:Micelles D018613:Microscopy, Confocal D009842:Oligopeptides D017239:Paclitaxel D011485:Protein Binding
Confocal microscopy cytotoxicity RGD peptide amphiphile fluorescence polarization micelle stability receptor-mediated endocytosis