Purpose: The goal of this study is to demonstrate the feasibility of chemically modified human adenovirus (Ad) vectors for tumor retargeting. Procedures: E1- and E3-deleted Ad vectors carrying firefly luciferase reporter gene under cytomegalovirus promoter (AdLuc) was surface-modified with cyclic arginine-glycine-aspartic acid (RGD) peptides through a bifunctional poly(ethyleneglycol) linker (RGD-PEG-AdLuc) for integrin αvβ3 specific delivery. The Coxsackie and adenovirus viral receptor (CAR) and integrin αvβ3 expression in various tumor cell lines was determined by reverse transcriptase PCR and fluorescence-activated cell sorting. Bioluminescence imaging was performed in vitro and in vivo to evaluate RGD-modified AdLuc infectivity. Results: RGD-PEG-AdLuc abrogated the native CAR tropism and exhibited significantly enhanced transduction efficiency of integrin-positive tumors than AdLuc through intravenous administration. Conclusion: This approach provides a robust platform for site-specific gene delivery and noninvasive monitoring of the transgene delivery efficacy and homing.
Bibliographical noteFunding Information:
Acknowledgments. This work was supported, in part, by National Institute of Biomedical Imaging and Bioengineering (R21 EB001785), National Cancer Institute (R21 CA102123, P50 CA114747, U54 CA119367, and R24 CA93862), Department of Defense (W81XWH-04-1-0697, W81XWH-06-1-0665, W81XWH-06-1-0042, and DAMD17-03-1-0143), and a Benedict Cassen Postdoctoral Fellowship from the Education and Research Foundation of the Society of Nuclear Medicine (to WC). GN and ZX contributed equally to this work.
- Bioluminescence imaging
- Firefly luciferase
- Integrin αβ
- Reporter gene