Novel therapeutic strategy for prevention of malignant tumor recurrence after surgery: Local delivery and prolonged release of adenovirus immobilized in photocured, tissue-adhesive gelatinous matrix.

Abstract

We have been developing a new gene delivery method using a styrenated gelatin-based tissue-adhesive matrix that allows in situ adenovirus-immobilized gel formation on living tissue and sustained virus release to permeate carcinoma tissue. Styrenated gelatin was synthesized by the condensation reaction of gelatin with 4-vinylbenzoic acid. Aqueous styrenated gelatin solution premixed with AdLacZ, adenovirus encoding beta-galactosidase cDNA, and carboxylated camphorquinone (CQ) as a photoinitiator was irradiated with visible light to form a styrenated gelatin gel. The in vitro adenovirus release from the styrenated gelatin gel to a medium strongly depended not on styrenated gelatin concentration but on CQ concentration. Maximal beta-galactosidase expression was observed on day 1, followed by a rapid decrease that continued up to 1 month for a styrenated gelatin gel prepared with a low styrenated gelatin concentration and a low CQ concentration. Dose-dependent reduced expression of beta-galactosidase activity with increasing CQ under photoirradiation was observed. AdLacZ-immobilized styrenated gelatin gel was formed on a hybrid tissue, which is a cell traction-induced collagenous gel entrapped with fibroblasts, and lacZ gene expression of fibroblasts in the hybrid tissue was observed for more than one month. The result of this in vitro model experiment implies that the tissue-adhesive styrenated gelatin may be applicable for the delivery of adenovirus encoding cDNA for tumor dormancy therapy into malignant tissue to prevent tumor recurrence after surgery when cDNA is properly selected.