An endoglin-targeted nano-framework to improve drug permeability and reprogram VDA-recruited macrophages for breast cancer immunotherapy.
4 affiliations
- 1Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, The School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
- 2Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore.
- 3Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.
- 4The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, 510140 Guangzhou, China.
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.
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BibTeX
@article{cen2026endoglintargeted,
title = {{An endoglin-targeted nano-framework to improve drug permeability and reprogram VDA-recruited macrophages for breast cancer immunotherapy.}},
author = {Yi Cen and Xiaocheng Ou and Ying Chen and Zhuofeng Li and Xinxuan Li and Baixue Yu and Xiayun Chen and Lingwen Ding and Hong Cheng and Yuqing Wang and Shiying Li},
journal = {Asian journal of pharmaceutical sciences},
year = {2026},
month = oct,
doi = {10.1016/j.ajps.2026.101207},
url = {https://europepmc.org/article/MED/42999503},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - An endoglin-targeted nano-framework to improve drug permeability and reprogram VDA-recruited macrophages for breast cancer immunotherapy.
AU - Yi Cen
AU - Xiaocheng Ou
AU - Ying Chen
AU - Zhuofeng Li
AU - Xinxuan Li
AU - Baixue Yu
AU - Xiayun Chen
AU - Lingwen Ding
AU - Hong Cheng
AU - Yuqing Wang
AU - Shiying Li
PY - 2026
DA - 2026/10/16
JO - Asian journal of pharmaceutical sciences
DO - 10.1016/j.ajps.2026.101207
UR - https://europepmc.org/article/MED/42999503
AB - 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.
SN - 1818-0876
SN - 2221-285X
ER -