Free and poly-methyl-methacrylate-bounded BODIPYs: photodynamic and antimigratory effects in 2D and 3D cancer models

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

Vertical distribution of 137Cs in the lacustrine areas and preliminary results of 7Be activity in snow samples at terra nova bay (antarctica)

137Cs activity in samples from lacustrine areas around the Italian base in Antarctica is reported as an integration of a previous work. Preliminary data of cosmogenic 7Be activity determined in snowfalls, total atmospheric depositions, soil and air particulate collected during the 1990–91 and 1991–92 Italian expeditions in Antarctica is presented. The results obtained point out the efficiency of snow in the processes of air particulate scavenging and provide useful information for the development of research in Antarctica in the study of air/snow transfer processes by means of natural radionuclides. © 1994 Gordon and Breach Science Publishers S. A

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

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

HSA-hijacking nanobinders built on bioresponsive prodrugs for combined cancer chemoimmunotherapy

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer still lacking effective treatment options. Chemotherapy in combination with immunotherapy can restrict tumor progression and repolarize the tumor microenvironment towards an anti-tumor milieu, improving clinical outcome in TNBC patients. The chemotherapeutic drug paclitaxel had been shown to induce immunogenic cell death (ICD), whereas inhibitors of the indoleamine 2,3-dioxygenase 1 (IDO1), whose expression is shared in immune regulatory and tumor cells, have been revealed to enhance the anti-tumor immune response. However, poor bioavailability and pharmacokinetic, off-target effects and hurdles in achieving therapeutic drug concentrations at the target tissue often limit the effectiveness of combination therapies. This work describes the development of novel biomimetic and carrier-free nanobinders (NB) loaded with both paclitaxel and the IDO1 inhibitor NLG919 in the form of bioresponsive prodrugs, and capable of hijacking human serum albumin (HSA). A fine tuning of the preparation conditions allowed to identify NB@5 as the best-performing prodrugs-based nanoformulation. Our data show that NB@5 effectively binds with HSA, demonstrating its protective role in the controlled release of drugs in vitro and suggesting that NB could exploit the protein as the endogenous vehicle for targeted delivery to the tumor site. Our study successfully demonstrates that the drugs encapsulated within the nanobinders are preferentially released under the altered redox conditions commonly found in the tumor microenvironment, thereby inducing cell death, promoting ICD, and inhibiting IDO1. This study highlights the potential of prodrugs-based nanobinders as a promising avenue for the targeted chemoimmunotherapy of TNBC