95
VEGF-Based Delivery of
Boron Therapeutics--SibTech, Inc.,
Dr. Joseph M. Backer, Principal
Investigator, jbacker@sibtech.com
Dr. Joseph M. Backer, Business
Official, jbacker@sibtech.com
DOE Grant No.
DE-FG02-02ER83520
Amount:
$749,288
Because
the growth of primary tumor and metastatic lesions beyond a few millimeters
requires formation of new blood vessels (angiogenesis), the targeted
delivery of cytotoxic drugs to growing tumor blood vessels may form the basis
for a highly selective cancer therapy.
Particularly attractive are two-step therapies that initially deliver
relatively non-toxic “prodrugs” that are subsequently activated at the sites
of angiogenesis. This project will develop a two-step therapy that relies on
the targeted delivery of non-toxic boron-10 (10B) to the tumor
vasculature. When
the site is irradiated with low-energy neutrons, they will be captured by the 10B
atoms, which will undergo nuclear fission and yield high-energy products that
destroy cells. Phase I constructed
and tested in vitro assembled nanovehicles for boron-10 delivery. These
nanovehicles carried a high capacity polymeric carrier for boron-10 that allows
a “loading” of 1120 boron atoms per every targeted molecule. The
assembled nanovehicles were shown to be non-toxic, capable of binding to
cellular receptors of vascular endothelial growth factor, and internalized by
targeted cells. Phase II will test
assembled targeted nanovehicles in animal tumor models. Novel,
high capacity assembled nanovehicles will be constructed that combine imaging
and therapeutic capabilities.
Commercial Applications and Other Benefits as described by awardee:
Targeted boron-10 therapeutics may provide an attractive alternative to
highly toxic systemic chemotherapy and radiotherapy of cancer.