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Research Project
Silk Sericin as an industrial wastewater with valuable biomedical potential
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Application of near-infrared light responsive biomaterials for improving the wound healing process: A review
Publication . Graça, Mariana F. P.; Moreira, André F.; Correia, I.J.
Despite aiming to improve the healing process, the wound dressings that have been developed thus far still present high production costs, uncontrolled drug delivery, and are unable to fully re-establish all features of native skin. In this field, the development of light-responsive dressings has been emerging due to the possibility of controlling the delivery of therapeutic agents both in time and space. Moreover, this strategy has also been explored to guide the materials’ polymerization/crosslinking, as well as to mediate therapeutic approaches based on photothermal or photodynamic effects. Among the different approaches, the utilization of near-infrared (NIR) light holds a high translational potential due to the minimal interactions with the biological components and higher penetration capacity in human tissues. In this way, different biomaterials responsive to NIR light have been produced and explored in the production of active wound dressings. Therefore, this review aims to provide an overview of the advantages of NIR light to the wound healing process, in particular, its thermal, photodynamic, photobiomodulation, and imaging potential. Furthermore, the antibacterial, drug-release, and cellular responses that can be obtained with the application of NIR-responsive wound dressings are also described focusing on its impact on the healing process.
Reduced graphene oxide–reinforced tricalcium phosphate/gelatin/chitosan light-responsive scaffolds for application in bone regeneration
Publication . Cabral, Cátia S. D.; Melo-Diogo, Duarte de; Ferreira, Paula; Moreira, André F.; Correia, I.J.
Bone is a mineralized tissue with the intrinsic capacity for constant remodeling. Rapid prototyping techniques, using biomaterials that mimic the bone native matrix, have been used to develop osteoinductive and osteogenic personalized 3D structures, which can be further combined with drug delivery and phototherapy. Herein, a Fab@Home 3D Plotter printer was used to promote the layer-by-layer deposition of a composite mixture of gelatin, chitosan, tricalcium phosphate, and reduced graphene oxide (rGO). The phototherapeutic potential of the new NIR-responsive 3D_rGO scaffolds was assessed by comparing scaffolds with different rGO concentrations (1, 2, and 4 mg/mL). The data obtained show that the rGO incorporation confers to the scaffolds the capacity to interact with NIR light and induce a hyperthermy effect, with a maximum temperature increase of 16.7 °C after under NIR irradiation (10 min). Also, the increase in the rGO content improved the hydrophilicity and mechanical resistance of the scaffolds, particularly in the 3D_rGO4. Furthermore, the rGO could confer an NIR-triggered antibacterial effect to the 3D scaffolds, without compromising the osteoblasts' proliferation and viability. In general, the obtained data support the development of 3D_rGO for being applied as temporary scaffolds supporting the new bone tissue formation and avoiding the establishment of bacterial infections.
Red blood cell membrane-camouflaged gold-core silica shell nanorods for cancer drug delivery and photothermal therapy
Publication . Rodrigues, Ana Carolina F.; Correia, I.J.; Moreira, André F.
Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents.
Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines’ circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles’ half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC 41 derived membranes promoted the neutralization of the AuMSS’ surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers.
Indeed, the in vitro data revealed that PEI/RBC-derived membranes’ functionalization also improved the nanoparticles’ cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies.
Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.
Hyaluronic acid-functionalized graphene-based nanohybrids for targeted breast cancer chemo-photothermal therapy
Publication . Lima-Sousa, Rita; Melo, Bruna L.; Mendonça, António; Correia, I.J.; Melo-Diogo, Duarte de
Nanomaterials’ application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines’ translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials’ surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics’ action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells’ viability to just 23 %, showcasing their potential chemo-photothermal therapy.
Simple preparation of POxylated nanomaterials for cancer chemo-PDT/PTT
Publication . Nave, Micaela; Costa, Francisco J. P.; Alves, Cátia; Sousa, Rita Lima; Melo, Bruna L.; Correia, I.J.; Diogo, Duarte de Melo
Near infrared (NIR) light-responsive nanomaterials hold potential to mediate combinatorial therapies targeting
several cancer hallmarks. When irradiated, these nanomaterials produce reactive oxygen species (photodynamic
therapy) and/or a temperature increase (photothermal therapy). These events can damage cancer cells and
trigger the release of drugs from the nanomaterials’ core. However, engineering nanomaterials for cancer chemophotodynamic/photothermal therapy is a complex process. First, nanomaterials with photothermal capacity are
synthesized, being then loaded with photosensitizers plus chemotherapeutics, and, finally functionalized with
polymers for achieving suitable biological properties. To overcome this limitation, in this work, a novel
straightforward approach to attain NIR light-responsive nanosystems for cancer chemo-photodynamic/
photothermal therapy was established. Such was accomplished by synthesizing poly(2-ethyl-2-oxazoline)-
IR780 amphiphilic conjugates, which can be assembled into nanoparticles with photodynamic/photothermal
capabilities that simultaneously encapsulate Doxorubicin (DOX/PEtOx-IR NPs). The DOX/PEtOx-IR NPs presented a suitable size and surface charge for cancer-related applications. When irradiated with NIR light, the
DOX/PEtOx-IR NPs produced singlet oxygen as well as a smaller thermic effect that boosted the release of DOX
by 1.7-times. In the in vitro studies, the combination of DOX/PEtOx-IR NPs and NIR light could completely ablate breast cancer cells (viability ≈ 4 %), demonstrating the enhanced outcome arising from the nanomaterials' chemo-photodynamic/photothermal therapy.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
3599-PPCDT
Funding Award Number
PTDC/BTA-BTA/0696/2020