Rational design of carbon-based nanoplatforms for the delivery of therapeutic agents: the impact of changing the support and the translocating agent on cell internalization and endosomal escape abilities

• Autores: Julián Daniel Torres Vanegas
• Directores de la Tesis: Luis Humberto Reyes Barrios (dir. tes.), Juan Carlos Cruz Jiménez (dir. tes.)
• Lectura: En la Universidad de los Andes (Colombia) ( Colombia ) en 2023
• Idioma: inglés
• Tribunal Calificador de la Tesis: Johann Faccelo Osma Cruz (presid.), Gregory W. Wiedman (presid.), Carolina Cardona Ramírez (presid.), Katy C. Kao (presid.)
• Enlaces
  • Tesis en acceso abierto en: hdl.handle.net
• Resumen

  • Nanotechnology has garnered increasing attention for its potential in developing novel diagnostic and therapeutic systems. Carbon-based nanomaterials, in particular, have become a focal point of research due to their exceptional physicochemical properties and benign biological interactions. The rational construction of nanomaterial-based delivery systems necessitates a comprehensive understanding of the challenges and prospects in developing innovative nanovehicles. Prior work conducted by our research group demonstrated that cell-penetrating nanoplatforms with high cellular coverage and endosomal escape rates could be achieved through the immobilization of translocating peptides.

    In this study, we developed a robust methodology for constructing carbon-based nanoplatforms through the conjugation of established and novel cell-penetrating peptides using various surface chemistries. Our nanoplatforms were successfully characterized through spectroscopic, microscopic, and thermal stability analyses. Moreover, biocompatibility assays confirmed their promising potential for implementation in preclinical stages. Cell internalization and endosomal escape analyses were conducted using confocal imaging, revealing that our nanoplatforms achieved near-complete cell internalization and exhibited endosomal escape rates ranging from 12-50% in Vero and THP-1 cells. This research lays the groundwork for the development of next-generation, carbon-based, cell-penetrating nanovehicles for the delivery of therapeutic agents. Future studies will aim to elucidate the intracellular trafficking pathways of the nanobioconjugates to access various cellular compartments.