Yuanxin Chen1, Xiujie Liu1, Yuan Hou1,2, Zhaogang Yang3, Christina A. Von Roemeling1, Yaqing Qie1, Zhao Hai1,4, Yifan Wang5, Wen Jiang5, Betty Y.S. Kim1
1Department of Neurosurgery, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
2Department of Orthopaedic Surgery Zhongshan Hospital Fudan University No. 180 Fenglin Rd Shanghai 200032 China
3Department of Chemical and Biomolecular Engineering Ohio State University 151 W. Woodruff Ave. Columbus OH 43210 USA
4Department of Neurosurgery West China Hospital No. 37th Guoxue Xiang Chengdu Sichuan 610041 China
5Department of Radiation Oncology University of Texas Southwestern Medical Center 2280 Inwood Rd Dallas TX 75390 USA
Tóm tắt
AbstractA major challenge in the development of cancer nanomedicine is the inability for nanomaterials to efficiently penetrate and deliver therapeutic agents into solid tumors. Previous studies have shown that tumor vasculature and extracellular matrix regulate the transvascular and interstitial transport of nanoparticles, both critical for successfully delivering nanomedicine into solid tumors. Within the malignant tumor microenvironment, blood vessels are morphologically abnormal and functionally exhibit substantial permeability. Furthermore, the tumor extracellular matrix (ECM), unlike that of the normal tissue parenchyma, is densely packed with collagen. These pathophysiological properties greatly impede intratumoral delivery of nanomaterials. By using an antivascular endothelial growth factor receptor antibody, DC101, and an antitransforming growth factor β1 (TGF‐β1) antibody, normalization of the tumor vasculature and ECM is achieved, respectively, in a syngeneic murine glioma model. This normalization effect results in a more organized vascular network, improves tissue perfusion, and reduces collagen density, all of which contribute to enhanced nanoparticle delivery and distribution within tumors. These findings suggest that combined vascular and ECM normalization strategies can be used to remodel the tumor microenvironment and improve nanomedicine delivery into solid tumors, which has significant implications for developing more effective combinational therapeutic strategies using cancer nanomedicine.
