Targeted Delivery of CBD-Loaded Poly (RGD) Proteinoid Nanoparticles for Antitumor Therapy

Background: Targeted nanoparticle (NP)-based drug delivery systems enable administration of non-soluble drugs and enhance their efficacy. The arginine-glycine-aspartic acid (RGD) motif is a known recognition site of integrins, and RGD receptors are overexpressed in tumors and their neovasculature and can be used as targets for tumor treatment. Cannabidiol (CBD), the main non-psychotropic phytocannabinoid of Cannabis sativa, exhibits various therapeutic effects and has antitumor properties. Encapsulation of CBD within poly(RGD) (P(RGD)) proteinoid NPs can overcome the poor solubility and bioavailability of CBD and target it to tumors in vivo. Methods: P(RGD) proteinoid polymer was synthesized from D- and L-amino acids by thermal step-growth polymerization. CBD was encapsulated within the proteinoid NPs by self-assembly process. CBD-loaded proteinoid NPs were characterized in terms of particle diameter and size distribution, drug loading, ζ-potential, cytotoxicity, drug release, and biodistribution as well as antitumor effect. Results: P(RGD) proteinoid polymer was obtained with high molecular weight and low polydispersity. CBD was successfully encapsulated in the proteinoid NPs. The results demonstrate significant tumor growth inhibition by CBD-loaded P(RGD) proteinoid NPs compared to free CBD solution. The targeted delivery of P(RGD) NPs to tumors in a xenograft mouse model significantly increases (p<0.05) the anticancer activity of CBD with respect to the free compound. Conclusions: CBD-loaded P(RGD) NPs can potentially be used for anticancer therapy owing to their in vivo targeting ability, suggesting a good strategy for colorectal and breast cancers.