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Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation
Published on: December 15, 2010
Modulation of anti-angiogenic activity using ultrasound-activated nutlin-loaded piezoelectric nanovectors
Özlem Şen1, Attilio Marino1, Carlotta Pucci1
1Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025, Pontedera, Italy.
Abstract:
Angiogenesis plays a fundamental role in tumor development, as it is crucial for tumor progression, metastasis development, and invasion. In this view, anti-angiogenic therapy has received considerable attention in several cancer types in order to inhibit tumor vascularization, and the progress of nanotechnology offers opportunities to target and release anti-angiogenic agents in specific diseased areas. In this work, we showed that the angiogenic behavior of human cerebral microvascular endothelial cells can be inhibited by using nutlin-3a-loaded ApoE-functionalized polymeric piezoelectric nanoparticles, which can remotely respond to ultrasound stimulation. The anti-angiogenic effect, derived from the use of chemotherapy and chronic piezoelectric stimulation, leads to disruption of tubular vessel formation, decreased cell migration and invasion, and inhibition of angiogenic growth factors in the presence of migratory cues released by the tumor cells. Overall, the proposed use of remotely activated piezoelectric nanoparticles could provide a promising approach to hinder tumor-induced angiogenesis.
Insights
This study demonstrates that piezoelectric nanoparticles loaded with nutlin-3a can remotely inhibit tumor angiogenesis. Ultrasound stimulation of these nanoparticles effectively reduces endothelial cell migration and vessel formation, offering a novel anti-cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Angiogenesis is vital for tumor growth, metastasis, and invasion.
- Anti-angiogenic therapies aim to inhibit tumor vascularization.
- Nanotechnology provides tools for targeted delivery of anti-angiogenic agents.
Purpose of the Study:
- To investigate the anti-angiogenic potential of nutlin-3a-loaded ApoE-functionalized polymeric piezoelectric nanoparticles.
- To evaluate the remote activation of these nanoparticles using ultrasound stimulation.
- To assess the impact on human cerebral microvascular endothelial cells.
Main Methods:
- Loading nutlin-3a into ApoE-functionalized polymeric piezoelectric nanoparticles.
- Utilizing ultrasound to stimulate the nanoparticles.
- Assessing the effects on endothelial cell tubular formation, migration, and invasion.
- Measuring angiogenic growth factor expression.
Main Results:
- Nutlin-3a-loaded piezoelectric nanoparticles inhibited angiogenic behavior in endothelial cells.
- Ultrasound stimulation remotely activated the anti-angiogenic effect.
- Disruption of tubular vessel formation, decreased cell migration and invasion observed.
- Inhibition of tumor-induced angiogenic growth factors confirmed.
Conclusions:
- Remotely activated piezoelectric nanoparticles offer a promising strategy to inhibit tumor-induced angiogenesis.
- This approach could lead to novel therapeutic strategies for cancer treatment.
- Targeted delivery and activation of anti-angiogenic agents show significant potential.
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