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Published on: December 15, 2010
Ultrasound-Controlled Nano-Oxygen Delivery Modulates Endothelial Cells to Enhance Tumor Perfusion
Yang Qin1, Yichen Liu2, Zhongqi Li1
1National Engineering Laboratory for Resource Developing of Endangered Chinese Crude Drugs in Northwest China, Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, #620 West Chang'an Road, Xi'an 710119, China.
Focused ultrasound and oxygen nanobubbles (ONB_FUS) normalize tumor vasculature, reducing hypoxia and enhancing chemotherapy. This approach targets specific tumor endothelial cell subsets for improved cancer treatment.
Area of Science:
- Oncology
- Biomedical Engineering
- Vascular Biology
Background:
- Vascular normalization is a key strategy in antitumor therapy.
- Clinical use of antiangiogenic agents is limited by drug tolerance and toxicity.
- Targeting tumor vasculature remains a challenge in cancer treatment.
Purpose of the Study:
- To investigate the efficacy of focused ultrasound-stimulating oxygen nanobubbles (ONB_FUS) in inducing tumor vascular normalization.
- To identify the specific tumor endothelial cell (TEC) populations responsive to ONB_FUS treatment.
- To evaluate the impact of ONB_FUS-mediated vascular normalization on drug delivery and chemotherapy efficacy.
Main Methods:
- Utilized focused ultrasound combined with oxygen nanobubbles (ONB_FUS) in preclinical models.
- Assessed tumor hypoxia, perfusion, microvascular density, and pericyte coverage.
- Performed single-cell RNA sequencing on tumor endothelial cells (TECs).
- Analyzed clinical tumor samples for TEC subpopulations and pathway activity.
Main Results:
- ONB_FUS effectively alleviated tumor hypoxia and induced vascular normalization, improving perfusion and pericyte coverage while reducing microvascular density.
- Key proangiogenic pathways (VEGFA, ANGPT2) were downregulated during the normalization window.
- Single-cell RNA sequencing identified capillary endothelial cells (CapECs), particularly the CapEC_Spp1+ subset, as the primary responsive population.
- Clinical samples confirmed elevated CapEC abundance and heightened pathway activity in high-proliferation CapECs.
Conclusions:
- ONB_FUS provides a spatiotemporally controllable method for vascular remodeling in tumors.
- This approach enhances intratumoral drug delivery and potentiates chemotherapy efficacy.
- Identification of distinct TEC subpopulations offers novel targets for precision antiangiogenic therapy.
