Work

An endoglin-targeted nano-framework to improve drug permeability and reprogram VDA-recruited macrophages for breast cancer immunotherapy

Year: 2026

Type: article

Abstract: Conventional vascular disrupting agent (VDA) therapy is limited by off-target toxicity and an inability to exploit high permeability, thus constraining self-enhancing drug delivery. Moreover, the immunosuppressive macrophages recruited by VDAs further diminish therapeutic efficacy. In this work, we develop an Endoglin-targeted Nano-Framework to Obtain Repolarized Cancer-associated macrophages and Enhanced permeability (designated ENFORCE) for breast cancer immunotherapy. ENFORCE incorporates an endoglin-targeting peptide for precise binding to tumor vasculature and co-delivers the vascular disrupting agent combretastatin A4 (CA4) together with the immunomodulator R848. Upon release, CA4 rapidly disrupts tumor vasculature, thereby amplifying the enhanced permeability and retention (EPR) effect and promoting subsequent ENFORCE accumulation. Concurrently, CA4-induced recruitment of immunosuppressive macrophages is counteracted by R848, which reprograms tumor-associated macrophages toward a pro-inflammatory M1 phenotype. This combination of vascular remodeling and immune reprogramming enhances the tumor retention and bioavailability of αCD47, thereby boosting systemic antitumor immunity and eradicating metastatic tumors without causing obvious systemic toxicity. Overall, this work establishes a promising targeted nano-framework that integrates vascular disruption with macrophage immunomodulation, concurrently enhancing drug delivery and potentiating antitumor immunotherapy.

Source: Asian Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ajps.2026.101207