Tumor-Targeted Poly(ArgGlyAsp) Nanocapsules for Personalized Cancer Therapy – In Vivo Study

The arginine-glycine-glutamic acid (RGD) sequence, an αvβ3 integrin recognition site, is overexpressed in malignancies and neovasculature, making it a potential therapeutic target. Herein, efficacy/safety of tumor-targeted RGD-based proteinoid nanocapsules (NCs) entrapping a synergistic combination of two drugs—palbociclib (Pal), a CDK4/6 inhibitor, and alpelisib (Alp), a P13K inhibitor, as a cancer treatment, is assessed. P(RGD) proteinoid polymers are produced by thermal step-growth polymerization of R, G, and D under an inert atmosphere. P(RGD) NCs, hollow and encapsulating 25 w% each of Pal and Alp, are formed by self-assembly of the proteinoid polymer. The encapsulation yields of Pal and Alp are 72% and 95%, respectively. Long-term stability, controlled release, cellular uptake,synergistic cytotoxicity, and induced cell death are evident from in vitro experiments. Findings from in vivo breast, colon and gastric patient-derived xenograft (PDX) mice experiments are consistent with the in vitro studies showing that the response to treatment with drug-loaded NCs is similar to that elicited by free drugs, with reduced side effects. The study demonstrates the potential clinical utility of P(RGD) NCs for cancer treatment.