Publicação
Chemically crosslinked Injectable hydrogels laden with graphene-based nanostructures for chemo-photothermal anticancer applications
| Resumo: | Breast cancer is among the foremost causes of mortality on a global scale, exemplifying the disease's resilience and adaptability. The conventional clinical approaches, notably encompassing surgery, radiotherapy, chemotherapy, and immunotherapy, present significant limitations: subpar efficacy and adverse events/side effects. In view of these challenges, it is crucial to develop innovative strategies that can contribute for reducing the mortality rates related to breast cancer. In recent years, strategies based on nanomaterials for chemo-photothermal therapy have started to light the path, showcasing promising results in cancer treatment. The unique physical and chemical properties of these nanomaterials enable the encapsulation of chemotherapeutic drugs as well as their journey into the tumor site. In turn, the optical features enable these nanomaterials to absorb light in the near-infrared (NIR) region, deploying a localized heat. The combined action of these two modalities (drug delivery and photoinduced heat) amplifies the destruction of cancer cells. However, the limited capacity of nanomaterials to reach the tumors, following systemic administration, continues to represent a significant impediment to its full therapeutic capacity. The pursuit for overcoming the systemic administration problems has led to the development of injectable in situ forming hydrogels. These injectable hydrogels have the capacity to encapsulate anticancer agents (including drugs and nanomaterials), and to deliver them locally into the tumors. Among these, injectable hydrogels formed in situ by chemical crosslinking have gained popularity due to their stability and greater control over structural and functional properties (e.g., degradation rate, swelling capacity). In particular, injectable in situ forming hydrogels crosslinked by Thiol-Maleimide reaction are emerging due to the advantageous features of this chemistry: chemo-selectivity and rapid kinetics. In this MSc dissertation, a chemically crosslinked injectable in situ forming hydrogel was developed based on the Thiol-Maleimide reaction between thiolated poly(acrylic acid) and 4-arm poly(ethylene glycol)-maleimide. This hydrogel was incorporated with dopamine-reduced graphene oxide (DOPA-rGO; nanosized photothermal agent) and Doxorubicin (DOX; chemotherapeutic drug), being exploited for the chemo-photothermal therapy of breast cancer. The assembled formulations exhibited injectability and capacity to gelate in situ through the Thiol-Maleimide reaction. The degradation studies highlighted the excellent integrity of the hydrogels. Furthermore, the incorporation of DOPA-rGO into the hydrogel enabled the attainment of a minimal and well-controlled swelling. As importantly, the inclusion of DOPA-rGO into the hydrogel allowed a high photothermal effect under NIR irradiation, that also enhanced the release of DOX by up to 1.5-times. In vitro tests displayed the hydrogels’ favorable cytocompatibility. Besides this, the hydrogels incorporating both DOPA-rGO and DOX generated an effect under NIR irradiation that reduced the breast cancer cells’ viability to just ≈25%, hence confirming their chemo-photothermal capacity. In summary, the injectable hydrogels developed in this dissertation, based on the Thiol-Maleimide reaction between thiolated poly(acrylic acid) and 4-arm poly(ethylene glycol)-maleimide, that incorporated DOPA-rGO and DOX, have showcased auspicious results for application in the chemo-phototherapy of breast cancer cells. |
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| Autores principais: | Cunha, João Pedro Rolo da |
| Assunto: | Hidrogel injetável Reação Tiol-Maleimida Terapia Quimio-fototérmica Cancro da mama Ácido poliacrílico Nanomateriais da família do grafeno Administração local Injectable hydrogel Thiol-Maleimide reaction Chemo-photothermal therapy Breast cancer Poly(acrylic acid) Graphene family nanomaterials Local delivery |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade da Beira Interior |
| Idioma: | inglês |
| Origem: | uBibliorum |
| Resumo: | Breast cancer is among the foremost causes of mortality on a global scale, exemplifying the disease's resilience and adaptability. The conventional clinical approaches, notably encompassing surgery, radiotherapy, chemotherapy, and immunotherapy, present significant limitations: subpar efficacy and adverse events/side effects. In view of these challenges, it is crucial to develop innovative strategies that can contribute for reducing the mortality rates related to breast cancer. In recent years, strategies based on nanomaterials for chemo-photothermal therapy have started to light the path, showcasing promising results in cancer treatment. The unique physical and chemical properties of these nanomaterials enable the encapsulation of chemotherapeutic drugs as well as their journey into the tumor site. In turn, the optical features enable these nanomaterials to absorb light in the near-infrared (NIR) region, deploying a localized heat. The combined action of these two modalities (drug delivery and photoinduced heat) amplifies the destruction of cancer cells. However, the limited capacity of nanomaterials to reach the tumors, following systemic administration, continues to represent a significant impediment to its full therapeutic capacity. The pursuit for overcoming the systemic administration problems has led to the development of injectable in situ forming hydrogels. These injectable hydrogels have the capacity to encapsulate anticancer agents (including drugs and nanomaterials), and to deliver them locally into the tumors. Among these, injectable hydrogels formed in situ by chemical crosslinking have gained popularity due to their stability and greater control over structural and functional properties (e.g., degradation rate, swelling capacity). In particular, injectable in situ forming hydrogels crosslinked by Thiol-Maleimide reaction are emerging due to the advantageous features of this chemistry: chemo-selectivity and rapid kinetics. In this MSc dissertation, a chemically crosslinked injectable in situ forming hydrogel was developed based on the Thiol-Maleimide reaction between thiolated poly(acrylic acid) and 4-arm poly(ethylene glycol)-maleimide. This hydrogel was incorporated with dopamine-reduced graphene oxide (DOPA-rGO; nanosized photothermal agent) and Doxorubicin (DOX; chemotherapeutic drug), being exploited for the chemo-photothermal therapy of breast cancer. The assembled formulations exhibited injectability and capacity to gelate in situ through the Thiol-Maleimide reaction. The degradation studies highlighted the excellent integrity of the hydrogels. Furthermore, the incorporation of DOPA-rGO into the hydrogel enabled the attainment of a minimal and well-controlled swelling. As importantly, the inclusion of DOPA-rGO into the hydrogel allowed a high photothermal effect under NIR irradiation, that also enhanced the release of DOX by up to 1.5-times. In vitro tests displayed the hydrogels’ favorable cytocompatibility. Besides this, the hydrogels incorporating both DOPA-rGO and DOX generated an effect under NIR irradiation that reduced the breast cancer cells’ viability to just ≈25%, hence confirming their chemo-photothermal capacity. In summary, the injectable hydrogels developed in this dissertation, based on the Thiol-Maleimide reaction between thiolated poly(acrylic acid) and 4-arm poly(ethylene glycol)-maleimide, that incorporated DOPA-rGO and DOX, have showcased auspicious results for application in the chemo-phototherapy of breast cancer cells. |
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