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Design and Characterization of pMyc/pMax Peptide-Coupled Gold Nanosystems for Targeting Myc in Prostate Cancer Cell
Samuel Longoria-García1, Celia N Sánchez-Domínguez1, Margarita Sánchez-Domínguez2
1Departamento de Bioquímica y Medicina Molecular, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey 64460, Mexico.
Abstract:
Myc and Max are essential proteins in the development of prostate cancer. They act by dimerizing and binding to E-box sequences. Disrupting the Myc:Max heterodimer interaction or its binding to E-box sequences to interrupt gene transcription represent promising strategies for treating cancer. We designed novel pMyc and pMax peptides from reference sequences, and we evaluated their ability to bind specifically to E-box sequences using an electrophoretic mobility shift assay (EMSA). Then, we assembled nanosystems (NSs) by coupling pMyc and pMax peptides to AuNPs, and determined peptide conjugation using UV-Vis spectroscopy. After that, we characterized the NS to obtain the nanoparticle's size, hydrodynamic diameter, and zeta potential. Finally, we evaluated hemocompatibility and cytotoxic effects in three different prostate adenocarcinoma cell lines (LNCaP, PC-3, and DU145) and a non-cancerous cell line (Vero CCL-81). EMSA results suggests peptide-nucleic acid interactions between the pMyc:pMax dimer and the E-box. The hemolysis test showed little hemolytic activity for the NS at the concentrations (5, 0.5, and 0.05 ng/µL) we evaluated. Cell viability assays showed NS cytotoxicity. Overall, results suggest that the NS with pMyc and pMax peptides might be suitable for further research regarding Myc-driven prostate adenocarcinomas.
Insights
Novel nanosystems (NSs) carrying pMyc and pMax peptides show potential for prostate cancer treatment by targeting Myc:Max interactions. These peptide-coupled gold nanoparticles (AuNPs) demonstrated specific E-box binding and cytotoxicity in cancer cells.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Research
Background:
- Myc and Max proteins are crucial in prostate cancer development, promoting tumor growth through dimerization and E-box binding.
- Targeting the Myc:Max interaction or its DNA binding is a key strategy for cancer therapy.
- Developing novel therapeutic agents to disrupt these oncogenic pathways is essential.
Purpose of the Study:
- To design and synthesize novel pMyc and pMax peptides.
- To create and characterize nanosystems (NSs) by conjugating these peptides to gold nanoparticles (AuNPs).
- To evaluate the efficacy and safety of these NSs in targeting Myc-driven prostate cancer.
Main Methods:
- Peptide design and synthesis.
- Electrophoretic mobility shift assay (EMSA) to assess peptide-E-box binding.
- UV-Vis spectroscopy for peptide conjugation confirmation.
- Nanoparticle characterization (size, hydrodynamic diameter, zeta potential).
- In vitro hemocompatibility and cytotoxicity assays on prostate cancer cell lines (LNCaP, PC-3, DU145) and a non-cancerous cell line (Vero CCL-81).
Main Results:
- EMSA confirmed peptide-nucleic acid interactions between the pMyc:pMax dimer and E-box sequences.
- Hemolysis tests indicated minimal hemolytic activity of the NSs at evaluated concentrations.
- Cell viability assays demonstrated NS-induced cytotoxicity in prostate cancer cell lines.
Conclusions:
- The developed NSs with pMyc and pMax peptides exhibit specific E-box binding and cytotoxic effects.
- These findings suggest the potential of these NSs as a therapeutic strategy for Myc-driven prostate adenocarcinomas.
- Further research is warranted to explore the therapeutic application of these peptide-conjugated nanosystems.
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