Melanocortin-1 receptor-targeting ultrasmall silica nanoparticles for dual-modality human melanoma imaging Journal Article

Authors: Chen, F.; Zhang, X.; Ma, K.; Madajewski, B.; Benezra, M.; Zhang, L.; Phillips, E.; Turker, M. Z.; Gallazzi, F.; Penate-Medina, O.; Overholtzer, M.; Pauliah, M.; Gonen, M.; Zanzonico, P.; Wiesner, U.; Bradbury, M. S.; Quinn, T. P.
Article Title: Melanocortin-1 receptor-targeting ultrasmall silica nanoparticles for dual-modality human melanoma imaging
Abstract: The poor prognosis associated with malignant melanoma has not changed substantially over the past 30 years. Targeted molecular therapies, such as immunotherapy, have shown promise but suffer from resistance and off-target toxicities, underscoring the need for alternative therapeutic strategies that can be used in combination with existing protocols. Moreover, peptides targeting melanoma-specific markers, like the melanocortin-1 receptor (MC1-R), for imaging and therapy exhibit high renal uptake that limits clinical translation. In the current study, the application of ultrasmall fluorescent (Cy5) silica nanoparticles (C′ dots), conjugated with MC1-R targeting alpha melanocyte stimulating hormone (αMSH) peptides on the polyethylene glycol (PEG) coated surface, is examined for melanoma-selective imaging. αMSH peptide sequences, evaluated for conjugation to the PEG-Cy5-C′ dot nanoparticles, bound to MC1-R with high affinity and targeted melanoma in syngenetic and xenografted melanoma mouse models. Results demonstrated a 10-fold improvement in MC1-R affinity over the native peptide alone following surface attachment of the optimal αMSH peptide. Systematic in vivo studies further demonstrated favorable in vivo renal clearance kinetics as well as receptor-mediated tumor cell internalization of as-developed radiolabeled particle tracers in B16F10 melanoma bearing mice. These findings highlight the ability of αMSH-PEG-Cy5-C′ dots to overcome previous hurdles that prevented clinical translation of peptide and antibody-based melanoma probes and reveal the potential of αMSH-PEG-Cy5-C′ dots for melanoma-selective imaging, image-guided surgery, and therapeutic applications. © 2017 American Chemical Society.
Keywords: melanoma; oncology; diagnosis; peptides; nanoparticles; silica; malignant melanoma; mammals; dermatology; clinical translation; image guided surgery; therapeutic strategy; therapeutic application; silica nanoparticles; c′ dots; target-or-clear; ultrasmall silica nanoparticle; αmsh peptide; surface attachment
Journal Title: ACS Applied Materials & Interfaces
Volume: 10
Issue: 5
ISSN: 1944-8244
Publisher: American Chemical Society  
Date Published: 2018-02-07
Start Page: 4379
End Page: 4393
Language: English
DOI: 10.1021/acsami.7b14362
PROVIDER: scopus
PMCID: PMC5803308
PUBMED: 29058865
Notes: Article -- Export Date: 1 March 2018 -- Source: Scopus
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