GOUSPILLOU Noémie : Optimization of Photoporation for Transfection of Complex Molecules in Living Cells

Résumé de thèse :

The dynamic landscape of oncology has been profoundly reshaped by the advent of gene and cell therapies, presenting promising avenues for cancer treatment. A cornerstone of this transformative era is cellular trans- fection, a fundamental process facilitating the controlled integration of genetic material into cells [1]. Current transfection techniques, employing vectors (such as AAV or chemical methods) or physical permeabilization (acoustic, electric), grapple with limitations tied to variable and often low transfection rates, cell-type depend- ency, genotoxicity concerns, and the restricted size of exogenous materials [2].

In response to these challenges, photoporation has emerged as an innovative and prospective method for achieving efficient genetic material transfection into eukaryotic cells, particularly within the realm of oncology. This groundbreaking approach addresses the deficiencies of conventional methods, demonstrating superior per- formance in terms of efficiency, minimal cytotoxicity, high throughput, and precision at the single-cell level [3]. By leveraging optically activated gold nanoparticles, this technique induces a controlled rise in temperature and initiates a cavitation regime, forming vapor nanobubbles that exert mechanical forces on the cell membrane, creating nanopores for enhanced transfection. This presentation delves into the intricacies of photoporation and showcases preliminary results that extend its transfection capabilities to large molecules [4]. Collaborating closely with cancer research teams, our research aims to surmount the existing limitations associated with con- ventional transfection techniques. Photoporation emerges as a rapid, precise, and cost effective solution for transfecting plasmids and other disruptive molecules, thus opening new therapeutic possibilities in the field of oncology. As we continue to unravel the potential of photoporation, we anticipate that this approach will con- tribute significantly to advancing gene and cell therapies for cancer treatment.

1. María L. Santana-Armas, C. Tros de Ilarduya, Strategies for cancer gene-delivery improvement by non-viral vectors, Int. J. Pharma. 596 120291 (2021).

2. C. Sheridan, Why gene therapies must go virus-free?, Nat. Biotech. 41 737 (2023).
3. J. Ramon et al., Vapor nanobubble-mediated photoporation constitutes a versatile intracellular delivery technology,

Curr. Opin. Colloid Interface 54 10145 (2021).

4. M. Layachi et al., Novel opto-fluidic drug delivery system for efficient cellular transfection, J. Nanobiotechnology 21 43 (2023).

Doctorant : GOUSPILLOU Noémie

Directeur de thèse : COURTADE Emmanuel, SPRIET Corentin