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- Development of Multifunctional Hydrogel for Cancer TherapyPublication . Sabino, Ivo João Viana; Correia, Ilídio Joaquim Sobreira; Diogo, Duarte Miguel de Melo; Alves, Cátia GomesBreast cancer continues to be one of the most frequently diagnosed cancers, having also one of the highest mortality rates among women. This scenario is justified by the limitations associated with the therapies currently used in the clinic (namely chemotherapy and radiotherapy), which present a low efficacy and non-specific toxicity. In this way, the development of innovative therapeutic strategies displaying a higher efficacy and safety is of paramount importance. Among the therapeutics under study, the Chemo-Photothermal Therapy (Chemo-PTT) mediated by nanomaterials has been showing promising results. This therapeutic modality explores the possible synergistic effects occurring between the nanomaterials mediated’ Near Infrared (NIR) light induced heating, as well as its drug delivery capacity. However, less than 1 % of nanoparticles become accumulated within tumor, after systemic administration. To address this limitation, the delivery of nanomaterials directly into the tumor site by injectable tridimensional polymeric matrices has recently started to be explored. In this MSc Dissertation, an injectable in situ forming ionotropically crosslinked chitosan-based hydrogel was developed. Then, Bovine Serum Albumin nanoparticles loaded with IR780 (photothermal agent; IR/BPN) and nanoparticles of D-a-Tocopheryl Polyethylene Glycol 1000 Succinate encapsulating Doxorubicin (chemotherapeutic agent; DOX/TPN) were incorporated within the hydrogel polymeric matrix in order to explore it in cancer Chemo-PTT. The results obtained reveal that the produced hydrogels (IR/BPN@Gel and IR/BPN+DOX/TPN@Gel) present suitable physicochemical properties to be used in cancer therapy. Upon NIR light exposure, the IR/BPN@Gel and IR/BPN+DOX/TPN@Gel produced a temperature increase of 9.2 °C and 9.0 °C, respectively, confirming their photothermal capacity. As importantly, the NIR-light exposure also increased the release of DOX from the hydrogel by 1.7 times. In the in vitro studies, the IR/BPN@Gel presented a cytocompatible behavior towards breast cancer and normal cells. Moreover, the combination of IR/BPN@Gel with NIR light (photothermal therapy) led to a 65 % reduction in the viability of breast cancer cells. On the other hand, the non-irradiated IR/BPN+DOX/TPN@Gel (chemotherapy) only diminished cancer cells viability by 15 %. In stark contrast, the Chemo-PTT mediated by IR/BPN+DOX/TPN@Gel reduced the cancer cells viability by about 91 %. Overall, these results demonstrate that IR/BPN+DOX/TPN@Gel is an injectable in situ forming hydrogel with great potential for the Chemo-PTT of breast cancer.
- Injectable in situ forming hydrogels incorporating dual-nanoparticles for chemo- photothermal therapy of breast cancer cellsPublication . Sabino, Ivo; Sousa, Rita Lima; Alves, Cátia; Melo, Bruna L.; Moreira, André F.; Correia, I.J.; Diogo, Duarte de MeloChemo-photothermal therapy (chemo-PTT) mediated by nanomaterials holds a great potential for cancer treatment. However, the tumor uptake of the systemically administered nanomaterials was recently found to be below 1 %. To address this limitation, the development of injectable tridimensional polymeric matrices capable of delivering nanomaterials directly into the tumor site appears to be a promising approach. In this work, an injectable in situ forming ionotropically crosslinked chitosan-based hydrogel co-incorporating IR780 loaded nanoparticles (IR/BPN) and Doxorubicin (DOX) loaded nanoparticles (DOX/TPN) was developed for application in breast cancer chemo-PTT. The produced hydrogels (IR/BPN@Gel and IR/BPN+DOX/TPN@Gel) displayed suitable physicochemical properties and produced a temperature increase of about 9.1 °C upon exposure to Near Infrared (NIR) light. As importantly, the NIR-light exposure also increased the release of DOX from the hydrogel by 1.7-times. In the in vitro studies, the combination of IR/BPN@Gel with NIR light (photothermal therapy) led to a reduction in the viability of breast cancer cells to 35 %. On the other hand, the non-irradiated IR/BPN+DOX/TPN@Gel (chemotherapy) only diminished cancer cells' viability to 85 %. In contrast, the combined action of IR/BPN+DOX/TPN@Gel and NIR light reduced cancer cells' viability to about 9 %, demonstrating its potential for breast cancer chemo-PTT
- The importance of spheroids in analyzing nanomedicine efficacyPublication . Mó, Inês; Sabino, Ivo; Melo-Diogo, Duarte de; Sousa, Rita Lima; Alves, Cátia; Correia, I.J.The use of nanomedicines for cancer treatment holds a great potential due to their improved efficacy and safety. During the nanomedicine preclinical in vitro evaluation stage, these are mainly tested on cell culture monolayers. However, these 2D models are an unrealistic representation of the in vivo tumors, leading to an inaccurate screening of the candidate formulations. To address this problem, spheroids are emerging as an additional tool to validate the efficacy of new therapeutics due to the ability of these 3D in vitro cancer models to mimic the key features displayed by in vivo solid tumors. In this review, the application of spheroids for the evaluation of nanomedicines' physicochemical properties and therapeutic efficacy is discussed.