Sequential Application of Anticancer Drugs Enhance Cell Death by Rewiring Apoptotic Signaling Networks

Technology

This invention presents a versatile chronic intracranial implant capable of delivering chemical and electrical therapy precisely and exclusively to the intended site of action in the brain.  The device is 12 cm long, approximately 200 µm in diameter, manufactured out of flexible borosilicate glass tubing, and coated in reinforcing metal layers and surface functionalized for improved biocompatibility.  The glass has three bores that run axially along the length of the device.  Two conduct fluid and the third houses one or more electrodes.  This configuration allows multiple drug solutions to be infused independently with precise temporal control with simultaneous electrical stimulation or probing.  A variety of functions can be readily selected without the need to modify the device.  Moreover, this combined control may reduce the amount of drug necessary for the treatment, reducing the risk of drug tolerance and systemic side effects.  

Problem Addressed

The circuit-based neurological disorders are due to a failure in communication between multiple brain areas as opposed to a deficit in a single brain area.  Hence, the treatment of circuit-based disorders is far more effective when targeted to normalize neural activity across a circuit instead of focusing treatment on a single neural tissue.  The brain uses both chemical and electrical methods of communication; therefore, combining chemically- and electrically-based therapeutic approaches has great potential for normalizing neural activity across brain circuits.  However, systemic administration of drugs frequently leads to drug tolerance and dose escalation.  Moreover, currently available micro-cannula devices have limited functions and are not scalable to larger animal models or to clinical applications.  Hence, a single device that is capable of delivering drugs while performing simultaneous electrical stimulation is needed to precisely tune neural activity.    

Advantages

• Significantly more robust and versatile than currently available devices.

• Possesses more diverse capabilities than existing devices while still minimizing size, and therefore invasiveness.

• Makes it possible for more efficient and cost-effective production of device
• More efficient treatment process with precise temporal control and simultaneous electrical stimulation, reducing the incidence of drug tolerance and systemic side effects.
• Custom tailorable to the needs of each patient.  

Publications

Sequential Application of Anticancer Drugs Enhances Cell Death by Rewiring Apoptotic Signaling Networks. Cell 149, no. 4 (May 11, 2012): 780–94.

"One-two Punch Knocks out Aggressive Breast Cancer Cells." MIT News, May 11, 2012.