Facilitating Repeat Intracarotid Injections in Mouse Models by a Novel Injection Site Repair Technique
March 15th, 2024
Repair of the intracarotid artery in a mouse model after injection returns blood flow to the artery without negatively impacting the distribution of the injected material. Injection site repair facilitates subsequent injections through the same artery and prevents cerebral ischemia in mouse strains that lack a complete Circle of Willis.
Our research focuses on developing novel biological therapies for glioblastoma, including agents such as oncolytic viruses, and microRNAs. A major reason why brain tumor therapeutics fail, is ineffective delivery to the tumor within the brain. So we focus on developing new delivery methods, including mesenchymal stem cells and exosomes, which can be delivered by intra-arterial injection.
Oncolytic viruses and immune cell therapies such as CAR T-cells and NK cells, have shown great promise in vitro, but delivery to tumors in vivo remains challenging. We have established a clinical endovascular neurosurgical oncology program, which is complemented by basic and translational research approaches that focus on intra-arterial delivery of brain tumor therapeutics. One of the biggest challenges is effectively delivering therapies to brain tumors.
Intratumoral delivery has been used with some agents, but has had limited success because re-injection is not feasible and the agent may not reach all parts of the tumor. We are addressing this issue through intra-arterial delivery of therapeutics. Previous methods of injection through the carotid artery have employed ligation of the injected artery, and resulted in ischemic stroke in some mouse models that do not have a complete circle of Willis.
We developed a method to repair the injection site, preventing this issue, and enabling subsequent re-injection within the same artery. For brain tumors, we will continue to develop mesenchymal stem cells as delivery vehicles for oncolytic viruses and exosomes to deliver therapeutic cargoes, including microRNAs. It is important to note that with both of these agents, intra-arterial injection is key to efficient delivery and therapeutic benefit.
Overview
This study develops a method for repairing the intracarotid artery in a mouse model, allowing for effective delivery of brain tumor therapeutics while preventing cerebral ischemia. The approach facilitates subsequent injections through the same artery without negatively impacting the distribution of injected materials.
Key Study Components
Area of Science
- Neuroscience
- Oncology
- Therapeutic Delivery
Background
- Brain tumor therapeutics often fail due to ineffective delivery.
- Previous methods of intra-arterial injection led to ischemic stroke in certain mouse models.
- Repairing the injection site can prevent complications and allow for re-injection.
- Mesenchymal stem cells and exosomes are explored as delivery vehicles.
Purpose of Study
- To develop a reliable method for intra-arterial delivery of brain tumor therapies.
- To prevent ischemic complications associated with previous injection methods.
- To enhance the therapeutic efficacy of oncolytic viruses and microRNAs.
Methods Used
- Injection of therapeutic agents via the carotid artery.
- Repair of the injection site to maintain blood flow.
- Utilization of mesenchymal stem cells and exosomes for drug delivery.
- Assessment of blood flow and distribution of injected materials.
Main Results
- The repair method successfully restored blood flow to the artery.
- Subsequent injections through the repaired artery were feasible.
- No negative impact on the distribution of injected materials was observed.
- The method prevented cerebral ischemia in mouse strains lacking a complete Circle of Willis.
Conclusions
- The developed repair method is effective for intra-arterial delivery of therapeutics.
- This approach may improve the efficacy of treatments for brain tumors.
- Future studies will focus on optimizing delivery vehicles and therapeutic agents.
