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  • Dextran-based hydrogels loaded with graphene nanosystems for cancer photothermal therapy
    Publication . Silva, Gonçalo Fernandes da; Diogo, Duarte Miguel de Melo; Correia, Ilídio Joaquim Sobreira; Ferreira, Paula Cristina Nunes
    Breast cancer is known as a devastating health condition that affects a large portion of the worldwide population, having tremendous impact on the physical and mental health of the affected people. In the clinic, the therapeutic approaches used for cancer treatment include surgery, chemotherapy or radiotherapy. However, these treatments can also induce severe side effects and may have a wavering efficacy, which inadvertently leads to pronounced mortality rates. Hence, safer and more effective anticancer therapeutic approaches must be attained. In recent years, researchers have leaned into exploring the potential of nanomaterials’ photothermal therapy for anticancer applications. Certain nanomaterials are capable of absorbing Near-Infrared (NIR; 750-1000nm) light, converting it into heat that thermally damages cancer cells. Still, these nanostructures are generally administered through systemic injection, having a limited capacity to reach the tumor site. Due to this limitation, new ways of administering nanoparticles into the tumor site are currently under investigation. Hydrogels are emerging due to their capacity to encapsulate NIR-responsive nanomaterials, as well as owing to their biocompatibility and biodegradability. As importantly, the nanoparticle-laden hydrogels can be locally inserted into the tumor, by injection or as a surgical implant, allowing a tumor-confined delivery of the NIR-responsive nanomaterials. For this application, hydrogels crosslinked by the Schiff-base reaction are also attracting the attention of researchers for cancer therapy, due to their simple formulation that relies on the mixture of polymers with carbonyl groups and polymers with primary amines. In this work, a novel Schiff-base crosslinked hydrogel was developed for application in cancer photothermal therapy. For such, the hydrogel was assembled by reacting Oxidized Dextran with branched poly(ethyleneimine) and branched (8-arm) poly(ethylene glycol)- NH2. Moreover, Dopamine-reduced Graphene Oxide (DOPA-rGO) was also incorporated into the hydrogel, during its assembly, for granting a photothermal capacity to the nanocomposite hydrogel. The obtained results showed that the hydrogel containing DOPA-rGO was assembled by the Schiff-base reaction and that it presented uniform macroscopic features. Furthermore, this formulation also presented a suitable degradability and a short-lived swelling. Upon NIR laser irradiation, the DOPA-rGO loaded Schiff-base hydrogel could produce an average temperature variation of 16 °C, confirming its photothermal capacity. The in vitro studies also highlighted the good cytocompatibility profile of the produced hydrogel towards both normal and breast cancer cells. As importantly, when the DOPA-rGO loaded Schiff-base hydrogel was exposed to NIR light, it generated a photothermal effect that reduced the breast cancer cells’ viability to just ≈ 27%. Overall, the produced DOPA-rGO loaded Schiff-base hydrogel is a novel and promising technology to be applied in the photothermal therapy of breast cancer cells.