Light-switchable diphtherin transgene system combined with losartan for triple negtative breast cancer therapy based on nano drug delivery system

Breast cancer is a common malignancy in women. The abnormally dense collagen network in breast cancer forms a therapeutic barrier that hinders the penetration and anti-tumor effect of drugs. To overcome this hurdle, we adopted a therapeutic strategy to treat breast cancer which combined a light-switchable transgene system and losartan. The light-switchable transgene system could regulate expression of the diphtheria toxin A fragment (DTA) gene with a high on/off ratio under blue light and had great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system to achieve tumor microenvironment-responsive and targeted delivery of DTA-encoded plasmids (pDTA) to tumor sites via dual targeting to cluster of differentiation-44 and alpha(v)beta(3) receptors. In vivo studies indicated that the combination of pDTA and losartan reduce the concentration of collagen type I from 5.9 to 1.9 mu g/g and decreased the level of active transforming growth factor-beta by 75.0% in tumor tissues. Moreover, deeper tumor penetration was achieved, tumor growth was inhibited, and the survival rate was increased. Our combination strategy provides a novel and practical method for clinical treatment of breast cancer.

Automated summary

The study presents a novel treatment strategy for overcoming the therapeutic barrier in breast cancer using a combination of a light-switchable transgene system and losartan. The researchers developed a nanoparticle drug delivery system for targeted and responsive delivery of therapeutic genes to tumor sites. In vivo studies showed improved tumor penetration, inhibited tumor growth, and increased survival rate. This combination strategy provides a promising method for clinical treatment of breast cancer.