Co-delivery of adenovirus and carmustine by anionic liposomes with synergistic anti-tumor effects

Abstract

Purpose: To improve gene transducibility mediated by adenovirus (Ad) in cancer cells and further enhance anti-tumor effects by co-delivery.

Methods: Calcium-induced phase change method was used to prepare the complex of anionic liposomes and adenovirus (AL/Ad5). Gene expression was qualitatively detected by X-gal staining and quantitatively detected by ELISA. Taking adenovirus-mediated stromal cell-derived factor-1α (Ad5-SDF1α) as therapeutic gene and carmustine (BCNU) as chemotherapeutic agent, a co-delivering system of AL/Ad5-SDF1α/BCNU was prepared and administered to tumor-bearing mice by intratumor injection.

Results: Enhanced LacZ gene transduction was obtained in B16 and Lewis lung carcinoma cells in vitro and in vivo. Complexes of AL/Ad5-SDF1α improved SDF1α gene expression and led to accumulation of dendritic cells among the murine B16 melanoma cells in vivo. This co-delivery system of AL/Ad5-SDF1α/BCNU could significantly suppress tumor growth and prolong survival of tumor-bearing mice.

Conclusions: Through the co-delivering system, AL/Ad5-SDF1α could synergize with BCNU to improve the antitumor effect. It may be a promising strategy for solid tumor therapy.