Organic Selenium induces ferroptosis in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDA) cells reprogram both mitochondrial and lysosomal functions to support growth. At the same time, this causes significant dishomeostasis of free radicals. While this is compensated by the upregulation of detoxification mechanisms, it also represents a potential vulnerability. Here we demonstrate that PDA cells are sensitive to the inhibition of the mevalonate pathway (MVP), which supports the biosynthesis of critical antioxidant intermediates and protect from ferroptosis. We attacked the susceptibility of PDA cells to ferroptotic death with selenorganic compounds, including dibenzyl diselenide (DBDS) that exhibits potent pro-oxidant properties and inhibits tumor growth in vitro and in vivo. DBDS treatment induces the mobilization of iron from mitochondria enabling uncontrolled lipid peroxidation. Finally, we showed that DBDS and statins act synergistically to promote ferroptosis and provide evidence that combined treatment is a viable strategy to combat PDA.

Curcumin and Graphene Oxide Incorporated into Alginate Hydrogels as Versatile Devices for the Local Treatment of Squamous Cell Carcinoma.

With the aim of preparing hybrid hydrogels suitable for use as patches for the local treatment of squamous cell carcinoma (SCC)-affected areas, curcumin (CUR) was loaded onto graphene oxide (GO) nanosheets, which were then blended into an alginate hydrogel that was crosslinked by means of calcium ions. The homogeneous incorporation of GO within the polymer network, which was confirmed through morphological investigations, improved the stability of the hybrid system compared to blank hydrogels. The weight loss in the 100-170 °C temperature range was reduced from 30% to 20%, and the degradation of alginate chains shifted to higher temperatures. Moreover, GO enhanced the stability in water media by counteracting the de-crosslinking process of the polymer network. Cell viability assays showed that the loading of CUR (2.5% and 5% by weight) was able to reduce the intrinsic toxicity of GO towards healthy cells, while higher amounts were ineffective due to the antioxidant/prooxidant paradox. Interestingly, the CUR-loaded systems were found to possess a strong cytotoxic effect in SCC cancer cells, and the sustained CUR release (~50% after 96 h) allowed long-term anticancer efficiency to be hypothesized.

Combined chemo-photothermal treatment of three-dimensional head and neck squamous cell carcinomas by gold nano-architectures.

Synergistic combined treatments are currently practiced in clinics for the management of several neoplasms. While surgery, radiotherapy, and chemotherapy remain as the standards of care for monomodal and co-treatments, emerging modalities like hyperthermia (HT) demonstrate promising features as (neo)adjuvant, particularly for recurrent cancers. However, the clinical relevance of HT is still debated due to a number of challenges, such as tumor specific temperature increase, uneven heating of the target, and the lack of agents that concurrently execute HT in combination with radio- and/or chemotherapy. Here, the application of non-persistent ultrasmall-in-nano gold architectures for synergistic chemo-photothermal treatment of head and neck squamous cell carcinomas (HNSCCs) is presented. The nano-architectures are composed of excretable narrow near-infrared (NIR)-absorbing gold ultrasmall nanoparticles and an endogenously double controlled cisplatin prodrug. The efficiency of the nano-architectures is evaluated on three-dimensional (3D) models of HNSCCs with positive or negative human papillomavirus (HPV) status. The combined treatment causes a more pronounced antitumor action on HPV-positive HNSCCs. Overall, the findings demonstrate the potential clinical relevance of translatable noble metal-based synergistic treatments in tumors management.

Cancer phototherapy in living cells by multiphoton release of doxorubicin from gold nanospheres.

Doxorubicin is a widely used but toxic cancer chemotherapeutic agent. In order to localize its therapeutic action and minimize side effects, it was covalently conjugated to peptide-encapsulated gold nanospheres by click-chemistry and then photo-released in a controlled fashion by a multiphoton process. Selective treatment of a chosen region in a 2D layer of U2Os cancer cells is shown by driving photorelease with 561 nm irradiation at µW power. These results show promising directions for the development of practical applications based on nanocarriers that can ensure drug delivery with high spatial and temporal control.