Resolution of Lymphedema with Induced Lymphangiogenesis Using Tissue Nanotransfection Technology
Abstract
This proposal addresses the FY20 PRMRP topic vascular malformations and the specific area of encouragement, “research to develop or improve methods to diagnose and manage vascular malformations, including, but not limited to, lymphatic, capillary, venous, and arteriovenous and hemangiomas.” Lymphedema is a chronic condition characterized by limb swelling. It is caused by dysfunctional lymphatic vessels, which bring fluid from the tissues back to the blood system. This results in the affected limb enlargement. It can be caused by malformed lymphatics at birth or more commonly from injury to the lymphatic system from trauma or cancer treatment. It is estimated that 5 million Americans have lymphedema. This condition affects 20%-40% of patients that undergo treatment for cancer, especially breast cancer. Bilateral lower extremity inflammatory lymphedema has been described in an epidemiologic study in Air Force basic trainees. Another common cause of lymphedema is an infection by the parasite Wuchereria bancrofti, which causes filariasis. Servicemen stationed in subtropics of Asia, Africa, the Western Pacific, Caribbean, and South America are vulnerable to this condition. Lymphatic filariasis was predominant in the Pacific during World War II. Patients with lymphedema have a large limb, which is prone to frequent infection, causes pain, and affects function. There is no cure for this disease. Treatment consists of compression (e.g., elastic stockings) and physical therapy. There are surgical treatments to remove extra abnormal tissue, but the excisional operations are morbid and do not reverse the problem. This proposal presents a novel nanotechnology approach to induce lymphangiogenesis (new lymphatic vessel development) to resolve lymphedema. This innovative method uses a chip with nanochannels in a rapid (<100ms) focused electric field to deliver lymphangiogenic genes through the skin directly to the affected site. This method of non-invasive gene delivery, termed tissue nanotransfection technology (TNT), has been successfully used for topical gene delivery. Traditional methods of gene therapy use viruses to facilitate delivery and have challenges with being used clinically to treat patients. TNT is non-viral and can be carried out topically in a localized area instead of traditional avenues of gene therapy, which usually act globally throughout the body. The expected goal of this proposal is that delivery of lymphangiogenic genes to promote new lymphatic vessel growth using the TNT nanotechnology chip will result in improvement of the lymphedema in the mouse tails. Clinical Impact: This innovative method can potentially establish innovative new treatment of lymphedema by using a non-invasive, portable nanochip (TNT) to deliver specific genes at the arm/leg with lymphedema. It can potentially by administered by a physician in a procedure room in a hospital or clinic setting.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110135
Entities
People
- Aladdin Hassanein
Organizations
- Indiana University
- United States Army