Novel BUF2-magnetite nanobioconjugates with cell-penetrating abilities

Abstract

Monica Cuellar,1 Javier Cifuentes,1 Jessica Perez,1 Alejandra Suarez-Arnedo,1 Julian A Serna,1 Helena Groot,2 Carolina Muñoz-Camargo,1 Juan C Cruz1 1Department of Biomedical Engineering, Universidad de los Andes, Bogotá, Colombia; 2Human Genetics Laboratory, Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia Introduction: One of the major challenges of modern pharmacology is the development of systems for the delivery of therapeutic molecules in a controlled and localized manner. One strategy is to use nanostructured supports, which are well suited to carry a large number of molecules on a per mass basis. A major challenge for these supports is, however, their limited ability to bypass the cell membrane. Recent studies propose that to overcome this issue, potent translocating cell-penetrating peptides (CPPs) can be conjugated to their surfaces. Methods: Here, we conjugated the antimicrobial CPP buforin II (BUF2) to the surface of magnetite nanoparticles to enhance their cell penetration. Conjugates were characterized via Fourier transform infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis, and their biocompatibility was corroborated. The conjugates were delivered in both bacterial and mammalian cells demonstrating the intracellular inclusion in THP-1 cells for the first time. Results: Despite the promising outcome, our studies showed that the obtained conjugates failed to maintain the native antimicrobial activity of BUF2. We hypothesize that to overcome this issue, a flexible linker can be inserted prior to conjugation. Conclusion: Our study highlights the potential of BUF2-magnetite conjugates as cell-penetrating vehicles for the targeted delivery of pharmacological agents. This provides support for the idea of a promising combined drug delivery and antimicrobial peptide therapy. Keywords: BUF2-magnetite, antimicrobial activity, cell-penetrating peptides, nanomaterials, drug delivery

Keywords

• BUF2-Magnetite
• antimicrobial activity
• Cell penetrating peptides
• nanomaterials
• drug delivery.