Inhibition of melanoma metastasis by dual-peptlde PLGA NPS

Inhibition of melanoma metastasis by dual-peptlde PLGA NPS

Author Arruda, Denise Costa Google Scholar
de Oliveira, Thais Dolzany Google Scholar
Fukuda Cursino, Patricia Harume Autor UNIFESP Google Scholar
Carneiro Maia, Vera Susana Google Scholar
Berzaghi, Rodrigo Autor UNIFESP Google Scholar
Travassos, Luiz R. Autor UNIFESP Google Scholar
Tada, Dayane Batista Autor UNIFESP Google Scholar
Abstract Despite the positive results observed in vitro and in vivo, clinical trials with bioactive peptides are generally hampered by their fast degradation in the biological system. Two bioactive peptides, P20 (CSSRTMHHC and the combined peptide C (CVNHPAFACGYGHTMYYHHYQHHL) have been identified as anticancer therapeutics. Combined peptide C consists of peptide C (CVNHPAFAC), a tumor-homing peptide, conjugated to the antiangiogenic peptide HTMYYHHYQHHL with a GYG. In this work, PLGA NPs with peptide C were applied as a dual-peptide carrier for application in cancer therapy. Peptide P20 was loaded into the NPs and combined peptide C was conjugated to the NPs surface. These NPs were evaluated as a therapeutic system to treat metastatic melanoma. in vivo assays showed that P20 encapsulation in PLGA NPs enhanced its antitumor activity. The inhibitory activity of P20-PLGANPs was similar to the activity of non-encapsulated P20 in a dose fivefold higher. The inhibitory activity was even higher when P20PLGA NPs were functionalized with combined peptide C. P20PLGAPepC NPs reduced in 28% the number of lung nodules in a syngeneic model of metastatic melanoma as compared to untreated animals. Additionally to the better tumor targeting and the in situ release of P20, it is expected that the therapeutic efficiency of the dual-peptide PLGA NPs was further enhanced by a synergistic effect between P20 and combined peptide C. Our encouraging results showed that by enabling the co-delivery of two peptides and promoting tumor targeting, PLGA NPs coupled with peptide C is a promising platform for peptide-based cancer therapy.
Keywords antitumor peptides
metastatic melanoma
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2011/23895-8
FAPESP: 2015/05980-9
FAPESP: 2010/51423-0
Date 2017
Published in Biopolymers. Hoboken, v. 108, n. 5, p. -, 2017.
ISSN 0006-3525 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent -
Access rights Closed access
Type Article
Web of Science ID WOS:000415937200001

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