Ella Itzhaki

Bar Ilan, Israel

Title: Tumor-targeted fluorescent proteinoid nanocapsules encapsulating synergistic drugs for personalized cancer therapy

---

Biography

.

Abstract

Personalized cancer treatment based on specific mutations offers targeted therapy and is preferred over "standard" chemotherapy. Proteinoid polymers produced by thermal step-growth polymerization of amino acids may form nanocapsules (NCs) that encapsulate drugs overcoming miscibility problems and allowing passive targeted delivery with reduced side effects. The arginine-glycine-glutamic acid (RGD) sequence is known for its preferential attraction to ?v?3 integrin, which is highly expressed on neovascular endothelial cells that support tumor growth.

Here, tumor-targeted RGD-based proteinoid NCs entrapping a synergistic combination of Palbociclib (Pal) and Alpelisib (Alp) were synthesized by self-assembly to induce a reduction of tumor cell growth in different types of cancers. The diameter and size distribution of the hollow and drug encapsulated polyRGD NCs used for the present work were 34 ± 5 and 22 ± 3 nm, respectively, thereby their drug targeted efficiency is  due to both passive and active targeting. The encapsulation yield of Pal and Alp was 70 and 90 %, respectively.  In vitro experiments with A549, MCF7 and HCT116 human cancer cells demonstrate a synergistic effect of Pal and Alp, controlled release, and dose-dependence. Preliminary results in a 3D tumor spheroid model with cells derived from patient-derived xenografts of colon cancer illustrate disassembly of spheroids, indicating that the NCs have therapeutic potential. Additional in vivo PDX mice experiments illustrated a significant reduction of tumor volume and reduced side effects compared to free drugs and hollow P(RGD) NCs. These results show the potential of the loaded NCs to stabilize cancerous tumors into becoming a chronic disease. This stabilization can greatly improve the survival rate of cancer patients.