Mesenchymal stem cells (MSCs) are perfect candidates for cell therapy against cancer due to their ability to migrate to damaged zones, especially to tumors (tumor-homing), besides other advantages such as their multipotent nature and their relatively easy isolation. However, their use is still limited by the success of the gene modification stage closely related to the vector used. Among the wide variety of vectors described, viral ones are still the most successful and one of the most spread in cell therapy are adenoviruses, in concrete, serotype 5 (Ad5). The problem with MSCs is that they are not susceptibles to infection by Ad5 due to the lack of Coxakievirus and Adenovirus Receptor (CAR), which hinders the effective interaction and internalization of these viruses. In this work, we have overcome that issue by coating adenoviruses with multifunctional 14-nm gold nanoparticles (AuNPs), decorated with different ligands to promote the efficient interaction between viruses and MSCs, improving the infection rate (Figure 1). The ligands studied have been RGD (known for attaching to integrins αvβ3 and αvβ5), zwitterionic groups such as azide, and quaternary ammonium groups used to provide positive net charge. Although the RGD motif has shown to be important, the positive net charge has been proven essential for more efficient interaction with MSCs membranes. Very promising results have been obtained using our vectors, three times better than with a commercial transfection agent, showing how these two gene vectors (adenoviruses and AuNPs) can be combined to get the most of both, the effectivity of Ad5 to replicate their genetic material in host cells, and the versatility of AuNPs to be multifunctionalized with selective ligands, opening a wide range of possibilities.

Multifunctionalized gold nanoparticles and adenoviruses, a perfect tandem for mesenchymal stem cells’ infection and cell therapy

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.