Magnetically guided viral transduction of gene-based sensitization for localized photodynamic therapy to overcome multi drug resistance in breast cancer cells

Chemotherapy represents a conventional treatment for many cancers at different stages either solely prescribed or concomitant to surgery and/or radiotherapy. However, treatment is tempered in instances of acquired drug... [ view full abstract ]

Chemotherapy represents a conventional treatment for many cancers at different stages either solely prescribed or concomitant to surgery and/or radiotherapy. However, treatment is tempered in instances of acquired drug resistance in response to either chemo- or targeted-therapy, leading to therapeutic failure. To overcome this challenge, many studies focus on how cancer cells manipulate their genomes and metabolism to prevent drug influx and/or facilitate efflux of accumulated chemo drugs. We previously developed ‘controllable’ virus’ for either recombinant adeno-associated virus serotype 2 (AAV2) via chemical conjugation with iron oxide nanoparticles that could be directed with magnetic fields. Furthermore, a gene of the photosensitive protein was introduced into the AAV2 genome to enable photo-dynamic therapy (PDT). In the case of PDT, irradiation with a specific light bandwidth generates reactive oxygen species leading to irreversible DNA damage and cell killing via an apoptotic pathway (Figure 1); offering additional options in cancer treatment. Here, we present an improvement to this previous work that promotes viral transduction in chemo drug resistant-MCF-7 (^CDRMCF-7) cells under magnetic field, and express the KillerRed (KR) protein in transduced cells for light-triggered virotherapy (AAV2-KR) (Figure 2). We have demonstrated highly efficient photosensitization with the gene-based KillerRed photosensitizer. Loco-regional specificity was achieved for viral transduction via utility of a magnetic field and conjugation of magnetic nanoparticles to the virus. This demonstrated successful anti-proliferation of chemotherapy drug resistant cancer cells. Such a technological model with improved virotherapy loco-regional specificity could be harnessed to overcome drug resistant cancer cells.