Rad51 protein is overexpressed in a wide range of human
cancers. Our previous in vitro studies demonstrated that a construct comprised Rad51 promoter driving expression of the
diphtheria toxin A gene (pRad51-
diphtheria toxin A (DTA)) destroys a variety of human
cancer cell lines, with minimal to no toxicity to normal human cells. Here we delivered Rad51 promoter-based constructs in vivo using linear
polyethylenimine nanoparticles, in vivo jetPEI, to visualize and treat
tumors in mice with HeLa xenografts. For
tumor detection, we used pRad51-Luc, a construct containing the
firefly luciferase under the Rad51 promoter, administered by intraperitoneal (IP) injection.
Tumors were detected with an in vivo bioluminescent camera. All mice with
cancer displayed strong bioluminescence, while mice without
cancer displayed no detectable bioluminescence. Treatment with pRad51-DTA/jetPEI decreased
tumor mass of subcutaneous (SC) and IP
tumors by sixfold and fourfold, respectively, along with the strong reduction of malignant
ascites. Fifty percent of the mice with SC
tumors were
cancer-free after six pRad51-DTA/jetPEI
injections, and for the mice with IP
tumors, mean survival time increased by 90% compared to control mice. This study demonstrates the clinical potential of pRad51-based constructs delivered by nanoparticles for the diagnostics and treatment of a wide range of
cancers.