4.7 Article

Metabolic Symbiosis-Blocking Nano-Combination for Tumor Vascular Normalization Treatment

Journal

ADVANCED HEALTHCARE MATERIALS
Volume 11, Issue 17, Pages -

Publisher

WILEY
DOI: 10.1002/adhm.202102724

Keywords

glycolysis inhibition; targeted drug delivery; tumor microenvironment remodeling; tumor vascular normalization treatment

Funding

  1. National Natural Science Foundation of China [81803457]
  2. China Postdoctoral Science Foundation Project [2020T130724, 2018M642378]
  3. Post-Doctoral Support of Jiangsu Province [2018Z063]
  4. Fundamental Research Funds for the Central Universities [2632021ZD10]

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By combining nanodrugs targeting the tumor microenvironment, this study enhances the efficacy of tumor vascular normalization treatment by inhibiting glycolysis in tumor cells and endothelial cells, leading to better antitumor effects.
The clinical anti-vascular endothelial growth factor (anti-VEGF) drugs and metronomic chemotherapy (MET) induced tumor vascular normalization treatment (TVNT) are easily antagonized by tumor microenvironment metabolic cross-talk between tumor cells and endothelial cells (ECs). To overcome this dilemma, nanodrug with the ability of ECs targeted glycolysis inhibition and nanodrug with the ability of tumor cell glycolysis inhibition, anti-VEGF, and MET are combined to prepare Nano-combination the pathways related to angiogenesis, tumor cell proliferation, and immunosuppression and breaking the negative sugar-lipid-protein metabolism balance in tumor microenvironment. Thus, stronger and more lasting normalized tumor vascular network and remarkable antitumor efficacy are obtained after treatment, constructing a positive feedback loop between TVNT and anti-tumor therapy. Above all, this study provides a new insight for solving the bottleneck of clinical TVNT.

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