Free and Poly-Methyl-Methacrylate-Bounded BODIPYs: Photodynamic and Antimigratory Effects in 2D and 3D Cancer Models

Simple Summary Photodynamic therapy (PDT) is a minimally invasive and highly selective technique to treat solid tumors and other malignancies. To exert a significant cytotoxic effect, PDT must simultaneously gather a photosensitizer (PS), a light at a specific wavelength, and oxygen. Although several PSs have been developed so far, systems with higher selectivity and efficacy are still needed to improve PDT anticancer treatment. This work shows how BODIPYs photosensitizers, loaded onto polymethyl methacrylate nanoparticles, can effectively reduce tumor cell viability in vitro and lower their migratory ability, thus, potentially reducing the metastatic tumor potential. Several limitations, including dark toxicity, reduced tumor tissue selectivity, low photostability and poor biocompatibility hamper the clinical use of Photodynamic therapy (PDT) in cancer treatment. To overcome these limitations, new PSs have been synthetized, and often combined with drug delivery systems, to improve selectivity and reduce toxicity. In this context, BODIPYs (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) have recently emerged as promising and easy-to-handle scaffolds for the preparation of effective PDT antitumor agents. In this study, the anticancer photodynamic effect of newly prepared negatively charged polymethyl methacrylate (nPMMA)-bounded BODIPYs (3@nPMMA and 6@nPMMA) was evaluated on a panel of 2D- and 3D-cultured cancer cell lines and compared with free BODIPYs. In particular, the effect on cell viability was evaluated, along with their ability to accumulate into the cells, induce apoptotic and/or necrotic cell death, and inhibit cellular migration. Our results indicated that 3@nPMMA and 6@nPMMA reduce cancer cell viability in 3D models of HC116 and MCF7 cells more effectively than the corresponding free compounds. Importantly, we demonstrated that MDA-MB231 and SKOV3 cell migration ability was significantly impaired by the PDT treatment mediated by 3@nPMMA and 6@nPMMA nanoparticles, likely indicating the capability of this approach to reduce metastatic tumor potential.

Automated summary

Photodynamic therapy (PDT) is a minimally invasive and highly selective technique for treating solid tumors and other malignancies. This study demonstrates that BODIPYs photosensitizers loaded onto polymethyl methacrylate nanoparticles can effectively reduce tumor cell viability and lower their migratory ability. These findings suggest that this approach has the potential to reduce the risk of metastatic tumors.