Hyaluronic acid-functionalized graphene-based nanohybrids for targeted breast cancer chemo-photothermal therapy.

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.

Injectable hydrogels for the delivery of nanomaterials for cancer combinatorial photothermal therapy.

Progress in the nanotechnology field has led to the development of a new class of materials capable of producing a temperature increase triggered by near infrared light. These photothermal nanostructures have been extensively explored in the ablation of cancer cells. Nevertheless, the available data in the literature have exposed that systemically administered nanomaterials have a poor tumor-homing capacity, hindering their full therapeutic potential. This paradigm shift has propelled the development of new injectable hydrogels for the local delivery of nanomaterials aimed at cancer photothermal therapy. These hydrogels can be assembled at the tumor site after injection (in situ forming) or can undergo a gel-sol-gel transition during injection (shear-thinning/self-healing). Besides incorporating photothermal nanostructures, these injectable hydrogels can also incorporate or be combined with other agents, paving the way for an improved therapeutic outcome. This review analyses the application of injectable hydrogels for the local delivery of nanomaterials aimed at cancer photothermal therapy as well as their combination with photodynamic-, chemo-, immuno- and radio-therapies.

Poly(2-ethyl-2-oxazoline) functionalized reduced graphene oxide: Optimization of the reduction process using dopamine and application in cancer photothermal therapy.

The high near infrared (NIR) absorption displayed by reduced graphene oxide (rGO) nanostructures renders them a great potential for application in cancer photothermal therapy. However, the production of this material often relies on the use of hydrazine as a reductant, leading to poor biocompatibility and environmental-related issues. In addition, to improve rGO colloidal stability, this material has been functionalized with poly(ethylene glycol). However, recent studies have reported the immunogenicity of poly(ethylene glycol)-based coatings. In this work, the production of rGO, by using dopamine as the reducing agent, was optimized considering the size distribution and NIR absorption of the attained materials. The obtained results unveiled that the rGO produced by using a 1:5 graphene oxide:dopamine weight ratio and a reaction time of 4 h (termed as DOPA-rGO) displayed the highest NIR absorption while retaining its nanometric size distribution. Subsequently, the DOPA-rGO was functionalized with thiol-terminated poly(2-ethyl-2-oxazoline) (P-DOPA-rGO), revealing suitable physicochemical features, colloidal stability and cytocompatibility. When irradiated with NIR light, the P-DOPA-rGO could produce a temperature increase (ΔT) of 36 °C (75 µg/mL; 808 nm, 1.7 W/cm2, 5 min). The photothermal therapy mediated by P-DOPA-rGO was capable of ablating breast cancer cells monolayers (viability < 3%) and could reduce heterotypic breast cancer spheroids' viability to just 30%. Overall, P-DOPA-rGO holds a great potential for application in breast cancer photothermal therapy.

Injectable in situ forming thermo-responsive graphene based hydrogels for cancer chemo-photothermal therapy and NIR light-enhanced antibacterial applications.

Functionalized graphene oxide (GO) and reduced GO (rGO) based nanomaterials hold a great potential for cancer photothermal therapy. However, their systemic administration has been associated with an accelerated blood clearance and/or with suboptimal tumor uptake. To address these limitations, the local delivery of GO/rGO to the tumor site by 3D matrices arises as a promising strategy. In this work, injectable chitosan-agarose in situ forming thermo-responsive hydrogels incorporating GO (thermogel-GO) or rGO (thermogel-rGO) were prepared for the first time. The hydrogels displayed suitable injectability and gelation time, as well as good physicochemical properties and cytocompatibility. When irradiated with near infrared (NIR) light, the thermogel-rGO produced a 3.8-times higher temperature increase than thermogel-GO, thus decreasing breast cancer cells' viability to 60%. By incorporating an optimized molar ratio of the Doxorubicin:Ibuprofen combination on thermogel-rGO, this formulation mediated a chemo-photothermal effect that further diminished cancer cells' viability to 34%. In addition, the hydrogels' antibacterial activity was further enhanced upon NIR laser irradiation, which is an important feature considering the possible risk of infection at the site of administration. Overall, thermogel-rGO is a promising injectable in situ forming hydrogel for combinatorial chemo-photothermal therapy of breast cancer cells and NIR light enhanced antibacterial applications.

An overview of electrospun membranes loaded with bioactive molecules for improving the wound healing process.

Nowadays, despite the intensive research performed in the area of skin tissue engineering, the treatment of skin lesions remains a big challenge for healthcare professionals. In fact, none of the wound dressings currently used in the clinic is capable of re-establishing all the native features of skin. An ideal wound dressing must confer protection to the wound from external microorganisms, chemical, and physical aggressions, as well as promote the healing process by stimulating the cell adhesion, differentiation, and proliferation. In recent years different types of wound dressings (such as films, hydrocolloids, hydrogels, micro/nano fibers) have been developed. Among them, electrospun nanofibrous membranes due to their intrinsic properties like high surface area-to-volume ratio, porosity and structural similarity with the skin extracellular matrix have been regarded as highly promising for wound dressings applications. Additionally, the nanofibers available in these membranes can act as drug delivery systems, which prompted the incorporation of biomolecules within their structure to prevent skin infections as well as improve the healing process. In this review, examples of different bioactive molecules that have been loaded on polymeric nanofibers are presented, highlighting the antibacterial biomolecules (e.g. antibiotics, silver nanoparticles and natural extracts-derived products) and the molecules capable of enhancing the healing process (e.g. growth factors, vitamins, and anti-inflammatory molecules).

In vitro characterization of 3D printed scaffolds aimed at bone tissue regeneration.

The incidence of fractures and bone-related diseases like osteoporosis has been increasing due to aging of the world's population. Up to now, grafts and titanium implants have been the principal therapeutic approaches used for bone repair/regeneration. However, these types of treatment have several shortcomings, like limited availability, risk of donor-to-recipient infection and tissue morbidity. To overcome these handicaps, new 3D templates, capable of replicating the features of the native tissue, are currently being developed by researchers from the area of tissue engineering. These 3D constructs are able to provide a temporary matrix on which host cells can adhere, proliferate and differentiate. Herein, 3D cylindrical scaffolds were designed to mimic the natural architecture of hollow bones, and to allow nutrient exchange and bone neovascularization. 3D scaffolds were produced with tricalcium phosphate (TCP)/alginic acid (AA) using a Fab@home 3D printer. Furthermore, graphene oxide (GO) was incorporated into the structure of some scaffolds to further enhance their mechanical properties. The results revealed that the scaffolds incorporating GO displayed greater porosity, without impairing their mechanical properties. These scaffolds also presented a controlled swelling profile, enhanced biomineralization capacity and were able to increase the Alkaline Phosphatase (ALP) activity. Such characteristics make TCP/AA scaffolds functionalized with GO promising 3D constructs for bone tissue engineering applications.

Recent advances on antimicrobial wound dressing: A review.

Skin and soft tissue infections (SSTIs) have high rates of morbidity and mortality associated. Despite the successful treatment of some SSTIs, those affecting the subcutaneous tissue, fascia, or muscle delay the healing process and can lead to life-threatening conditions. Therefore, more effective treatments are required to deal with such pathological situations. Recently, wound dressings loaded with antimicrobial agents emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this review, an overview of the most prominent antibacterial agents incorporated in wound dressings along with their mode of action is provided. Furthermore, the recent advances in the therapeutic approaches used in the clinic and some future perspectives regarding antibacterial wound dressings are also discussed.

3D Printed scaffolds with bactericidal activity aimed for bone tissue regeneration.

Nowadays, the incidence of bone disorders has steeply ascended and it is expected to double in the next decade, especially due to the ageing of the worldwide population. Bone defects and fractures lead to reduced patient's quality of life. Autografts, allografts and xenografts have been used to overcome different types of bone injuries, although limited availability, immune rejection or implant failure demand the development of new bone replacements. Moreover, the bacterial colonization of bone substitutes is the main cause of implant rejection. To vanquish these drawbacks, researchers from tissue engineering area are currently using computer-aided design models or medical data to produce 3D scaffolds by Rapid Prototyping (RP). Herein, Tricalcium phosphate (TCP)/Sodium Alginate (SA) scaffolds were produced using RP and subsequently functionalized with silver nanoparticles (AgNPs) through two different incorporation methods. The obtained results revealed that the composite scaffolds produced by direct incorporation of AgNPs are the most suitable for being used in bone tissue regeneration since they present appropriate mechanical properties, biocompatibility and bactericidal activity.