Delivery of Cancer-Testis Antigens Using Self-Assembled Dipeptide Nanotubes Inhibits Tumor Growth in Mice Melanoma Model

Abstract

Delivery of tumor-associated antigens for cancer immunotherapy is generally limited due to poor stability and low cellular uptake. Use of nanoparticles as delivery vehicles has been an exciting development but toxicity associated with nanoparticles has remained a concern. Here, we have used conformationally constraint self-assembling dipeptide nanotubes for the delivery of Cancer-Testis antigens (CTAs). A dipeptide Phenylalanine-α, β-dehydrophenylalanine (F-ΔF) was synthesized and was found to self-assemble into nanotubes. CTAs (NY-ESO-1 and MAGE-3) were also synthesized and loaded onto F-ΔF nanotubes using physical adsorption method for delivery purposes. CTA loaded F-ΔF nanotubes showed higher cellular uptake in macrophages. In animal studies, F-ΔF-CTA nanocomplex elicited much higher immune response compared to CTAs alone and showed an inhibition of ~65-70% tumor growth in mouse melanoma model. Our results indicated that F-ΔF nanotubes are biocompatible and are efficient delivery vehicles for CTAs in vivo and therefore are excellent candidates for further development as delivery agents.