iRGD-DOX-oHA-PLNs

iRGD-DOX-oHA-PLNs is an integrin-targeted polymer-lipid nanoparticle (PLN) system designed for the treatment of triple-negative breast cancer (TNBC). Developed by researchers at the University of Toronto, this multifunctional nanotherapeutic co-delivers the chemotherapeutic agent doxorubicin (DOX) and oligomeric hyaluronic acid (oHA). The nanoparticles are functionalized with the tumor-penetrating iRGD peptide, which targets integrins αvβ3 and αvβ5 expressed on tumor cells and cancer-associated fibroblasts (CAFs). Once internalized, oHA engages CD44 receptors, disrupting HA-CD44/RHAMM interactions and suppressing oncogenic MAPK/ERK signaling, which downregulates DNA repair proteins (such as RAD51, RAD50, and PARP1) and the drug efflux pump P-glycoprotein (P-gp). This synergistic action enhances doxorubicin-induced DNA damage, promotes immunogenic cell death, and reduces PD-L1 expression, thereby inhibiting primary tumor growth and preventing metastasis in both BRCA-mutant and wild-type TNBC models.

Other names

iRGD-DOX-oHA-PLN