Browsing by Author "Silva, Cleide Isabel Pais"
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- D-α-tocopheryl polyethylene glycol 1000 succinate functionalized nanographene oxide for cancer therapyPublication . Diogo, Duarte Miguel de Melo; Silva, Cleide Isabel Pais; Costa, Elisabete C.; Louro, Ricardo; Correia, Ilídio Joaquim SobreiraAim: To evaluate the therapeutic capacity of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized nanographene oxide (nGO) in breast cancer cells. Methods: TPGS-functionalized nGO-based materials were obtained through two different approaches: a simple sonication method and a one-pot hydrothermal treatment. Results: TPGS coating successfully improved the stability of the nGO-based materials. The nanomaterials that underwent the hydrothermal procedure generated a 1.4- to 1.6-fold higher temperature variation under near infrared laser irradiation than those prepared only by sonication. In vitro, the TPGS/nGO derivatives reduced breast cancer cells’ viability and had an insignificant effect on healthy cells. Furthermore, the combined application of TPGS/nGO derivatives and near infrared light generated an improved therapeutic effect. Conclusion: TPGS/nGO derivatives are promising materials for breast cancer phototherapy.
- Desenvolvimento de nanomateriais para a terapia fototermal do cancroPublication . Silva, Cleide Isabel Pais; Correia, Ilídio Joaquim Sobreira; Diogo, Duarte Miguel de MeloBreast cancer is one of the most prevalent and one of the leading causes of cancer-related deaths among women worldwide. In the specific case of the Portuguese population, breast cancer incidence and mortality rates increased in the past years. This scenario is mostly owed to the ineffectiveness of the currently available treatments (surgery, radiotherapy and small molecule-based therapies), whose therapeutic success is hindered by safety issues, non-specific toxicity and resistance mechanisms displayed by cancer cells to drugs. Such emphasizes the demand for a plethora of novel therapeutic approaches. In the past decades, light-induced therapies have started to be investigated as alternative strategies to combat cancer. These treatment modalities comprise photodynamic therapy (PDT) and photothermal therapy (PTT). Both therapeutic approaches depend on the external irradiation of the tumor region with near-infrared (NIR) light for activating photosensitizers or photothermal agents, that lead to the generation of reactive oxygen species (ROS; in PDT) or to a temperature increase (in PTT), which have a cytotoxic effect on cancer cells. Yet, such treatments still need to be further improved in what concerns their efficacy and selectivity towards the tumor region. Recently, the entrapment of NIR photoabsorbers in nanoparticles surpassed problems like the poor solubility of these molecules in biological fluids. Moreover, nanoparticles due to their physicochemical properties can display a preferential tumor accumulation, which is crucial for increasing the loaded NIR photoabsorbers bioavailability and ultimately the efficacy and selectivity of this therapeutic approach. Herein, a novel nanovehicle loaded with a NIR dye aimed for breast cancer phototherapy was developed. To accomplish that, two vitamin E derivatives, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and D-α-tocopheryl succinate (TOS), were used to assemble amphiphilic micelles with a core-shell structure. TPGS and TOS were selected due to their intrinsic anticancer activity (e.g. through the generation of ROS) and ability to encapsulate poorly water-soluble molecules. 2-[2-[2-Chloro-3-[(1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene]-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-propylindolium iodide (IR780) was chosen due to its versatile nature as a NIR light-responsive compound (photothermal agent, photosensitizer and NIR imaging dye). IR780-loaded TPGS-TOS micelles (IR780-TTM) with suitable sizes were obtained by using specific TPGS and TOS weight feed ratios during micelles formulation and these were able to encapsulate IR780 with high efficiency. In in vitro assays, the IR780-TTM induced a cytotoxic effect in cancer cells upon exposure to NIR irradiation through the generation of reactive oxygen species (PDT). This effective ablation of cancer cells was achieved using an ultra-low IR780 concentration. Moreover, IR780-TTM also demonstrated the ability to act as photothermal and imaging agents. Overall, the novel micellar nanoplatforms developed in this study possess a huge potential for breast cancer PDT. Moreover, IR780-TTM also demonstrate promising results to act as photothermal and imaging agents, which widens their applicability for the treatment and diagnosis of cancer.
- IR780-loaded TPGS-TOS micelles for breast cancer photodynamic therapyPublication . Silva, Cleide Isabel Pais; Diogo, Duarte Miguel de Melo; Correia, Ilídio Joaquim SobreiraIR780 iodide is a near-infrared (NIR) dye with a huge potential for cancer imaging and phototherapy. However, its biomedical application is strongly impaired by its lipophilic character. Herein, amphiphilic micelles based on d-α-tocopheryl polyethylene glycol succinate (TPGS) and d-α-tocopheryl succinate (TOS), two vitamin E derivatives with intrinsic anticancer activity, are explored to load IR780. IR780-loaded micelles with suitable sizes are obtained by using specific TPGS and TOS weight feed ratios during micelles formulation and these are able to encapsulate IR780 with high efficiency. In in vitro assays, the IR780-loaded micelles induce a cytotoxic effect in cancer cells upon exposure to NIR irradiation through the generation of reactive oxygen species (photodynamic therapy). This effective ablation of cancer cells is achieved using an ultra-low IR780 concentration. Moreover, IR780-loaded micelles also have the ability to act as photothermal and imaging agents, which widens their therapeutic and diagnostic potential. Overall, TPGS-TOS micelles are promising nanoplatforms for IR780-mediated cancer phototherapy and imaging.
- Strategies to Improve Cancer Photothermal Therapy Mediated by NanomaterialsPublication . Diogo, Duarte Miguel de Melo; Silva, Cleide Isabel Pais; Dias, Diana Rodrigues; Moreira, André; Correia, Ilídio Joaquim SobreiraThe deployment of hyperthermia‐based treatments for cancer therapy has captured the attention of different researchers worldwide. In particular, the application of light‐responsive nanomaterials to mediate hyperthermia has revealed promising results in several pre‐clinical assays. Unlike conventional therapies, these nanostructures can display a preferential tumor accumulation and thus mediate, upon irradiation with near‐infrared light, a selective hyperthermic effect with temporal resolution. Different types of nanomaterials such as those based on gold, carbon, copper, molybdenum, tungsten, iron, palladium and conjugated polymers have been used for this photothermal modality. This progress report summarizes the different strategies that have been applied so far for increasing the efficacy of the photothermal therapeutic effect mediated by nanomaterials, namely those that improve the accumulation of nanomaterials in tumors (e.g. by changing the corona composition or through the functionalization with targeting ligands), increase nanomaterials' intrinsic capacity to generate photoinduced heat (e.g. by synthesizing new nanomaterials or assembling nanostructures) or by optimizing the parameters related to the laser light used in the irradiation process (e.g. by modulating the radiation wavelength). Overall, the development of new strategies or the optimization and combination of the existing ones will surely give a major contribution for the application of nanomaterials in cancer PTT.