Inhibition of melanoma metastasis by dual-peptlde PLGA NPS

Author(s)

Arruda, Denise Costa ^[1] ; de Oliveira, Thais Dolzany ^[1] ; Fukuda Cursino, Patricia Harume ^[2] ; Carneiro Maia, Vera Susana ^[3] ; Berzaghi, Rodrigo ^[4] ; Travassos, Luiz R. ^[4] ; Tada, Dayane Batista ^[2]

Affiliation

^[1] Univ Mogi das Cruzes, Integrated Grp Biotechnol, Mogi das Cruzes, SP - Brazil

^[2] Univ Fed Sao Paulo, Inst Sci & Technol, Sao Jose Dos Campos, SP - Brazil

^[3] Recepta Biopharma, BR-04533 Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo UNIFESP, Expt Oncol Unit UNONEX, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Biopolymers; v. 108, n. 5 SEP 2017.
• Web of Science Citations: 1

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. (AU)

• FAPESP's process: 11/23895-8 - Characterization and control of cellular internalization process of nanoparticles
• Grantee: Dayane Batista Tada
• Support type: Research Grants - Young Investigators Grants
• FAPESP's process: 10/51423-0 - Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer
• Grantee: Luiz Rodolpho Raja Gabaglia Travassos
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 15/05980-9 - Antitumoral activity induced by peptides from transcription factor Brn-2 in murine and human melanoma
• Grantee: Denise Costa Arruda
• Support type: Regular Research Grants