Coating an adenovirus with functionalized gold nanoparticles favors uptake, intracellular trafficking and anti-cancer therapeutic efficacy
R González-Pastor(1) Y Hernández(2) M Gimeno(2) A de Martino(1) Y K.S Man(3) G Hallden(3) M Quintanilla(4) J M Fuente(2) P Martin-Duque(1,2,5,6)
1:Instituto Aragonés de Ciencias de la Salud; 2:Universidad de Zaragoza; 3:Queen Mary University; 4:IIB Alberto Sols (CSIC); 5:IIS Aragón; 6:Fundación Araid
Adenoviral (Ad) vectors have proven to be important tools for gene and cell therapy, although some issues still need to be addressed. In the past years, several organic and inorganic materials have been developed to reduce immunogenicity and improve biodistribution of Ad vectors. Here, we investigated the influence of the functionalization of 14 nm PEGylated gold nanoparticles (AuNPs) with quaternary ammonium groups and an arginine-glycine-aspartic acid (RGD)-motif on the uptake and biodistribution of Ad vectors.
We report the formation of Ad@AuNPs complexes that promote cell attachment and uptake, independently of the presence of the coxsackievirus receptor (CAR) and αv β₃ and αv β₅ integrins, significantly improving transduction without limiting Ad bioactivity. Besides, the presence of the RGD peptide favors tumor targeting and decreases Ad sequestration in the liver. Additionally, tumor delivery of a coated Ad vector expressing the human sodium iodide symporter (hNIS) by mesenchymal stem cells induces increased accumulation of radioactive iodine (¹³¹I) and tumor volume reduction compared to naked Ad-hNIS, highlighting the promising potential of our coating formulation in cancer gene therapy.
ACKNOWLEDGEMENTS: This research was supported by Instituto de Salud Carlos III (ISCIII) (PI19/01007 and DTS21/00130).