iRGD-DOX-oHA-PLN

iRGD-DOX-oHA-PLN is an investigational, tumor-penetrating, and multitargeted polymer-lipid nanoparticle (PLN) formulation developed by researchers at the University of Toronto. The nanoparticle is co-loaded with the chemotherapeutic agent doxorubicin (DOX) and oligomeric hyaluronic acid (oHA), and functionalized with the tumor-penetrating iRGD peptide. This system is designed to target integrins αvβ3 and αvβ5 on both triple-negative breast cancer (TNBC) cells and cancer-associated fibroblasts (CAFs) via the iRGD peptide, facilitating enhanced cellular uptake and deep tumor penetration. Once inside the tumor microenvironment, oHA binds to and blocks the native hyaluronic acid receptors CD44 and RHAMM, which downregulates DNA damage repair pathways (such as RAD50, RAD51, and PARP1) and suppresses PD-L1 expression. Concurrently, doxorubicin intercalates into DNA and inhibits topoisomerase II, leading to synergistic DNA double-strand breaks and immunogenic cell death. In preclinical models of both BRCA1-mutant and wild-type metastatic TNBC, iRGD-DOX-oHA-PLN has demonstrated superior efficacy in reducing primary tumor growth and preventing lung and liver metastasis compared to the PARP inhibitor olaparib.

Other names

iRGD-DOX-oHA-PLNsiRGD-functionalized polymer-lipid hybrid nanoparticle loaded with doxorubicin and oligomeric hyaluronic acid