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Poly(2-ethyl-2-oxazoline)–IR780 conjugate nanoparticles for breast cancer phototherapy

Publication . Alves, Cátia; Lima-Sousa, Rita; Melo, Bruna L.; Ferreira, Paula; Moreira, André; Correia, I.J.; de Melo-Diogo, Duarte

Conventional anticancer approaches are often associated with severe side effects. Herein, the authors assembled a novel nanoparticle whose therapeutic effect is triggered by laser light. In in vitro assays, the produced nanomaterial was able to, after interacting with laser light, reduce the viability of classic and advanced cancer models. In these conditions, but in the absence of laser light, no cytotoxicity was observed. In this way, the on-demand effect (triggered by laser light) may contribute to reduced side effects. Moreover, the produced nanoparticle revealed good stability, which is important for its future translation.

2023-02-21Journal article

Embargoed access

Reduced graphene oxide-enriched chitosan hydrogel/cellulose acetate-based nanofibers application in mild hyperthermia and skin regeneration

Publication . Graça, Mariana F. P.; Melo, Bruna L.; Sousa, Rita Lima; Ferreira, Paula; Moreira, André; Correia, I.J.

Asymmetric wound dressings have captured researchers' attention due to their ability to reproduce the structural and functional properties of the skin layers. Furthermore, recent studies also report the benefits of using near infrared (NIR) radiation-activated photothermal therapies in treating infections and chronic wounds. Herein, a chitosan (CS) and reduced graphene oxide (rGO) hydrogel (CS_rGO) was combined with a polycaprolactone (PCL) and cellulose acetate (CA) electrospun membrane (PCL_CA) to create a new NIR-responsive asymmetric wound dressing. The rGO incorporation in the hydrogel increased the NIR absorption capacity and allowed a mild hyperthermy effect, a temperature increase of 12.4 ◦C when irradiated with a NIR laser. Moreover, the PCL_CA membrane presented a low porosity and hydrophobic nature, whereas the CS_rGO hydrogel showed the ability to provide a moist environment, prevent exudate accumulation and allow gaseous exchanges. Furthermore, the in vitro data demonstrate the capacity of the asymmetric structure to act as a barrier against bacteria penetration as well as mediating a NIR-triggered antibacterial effect. Additionally, human fibroblasts were able to adhere and proliferate in the CS_rGO hydrogel, even under NIR laser irradiation, presenting cellular viabilities superior to 90 %. Altogether, our data support the application of the NIR-responsive asymmetric wound dressings for skin regeneration.

2022-12-29Journal article

Open access

Sulfobetaine methacrylate-coated reduced graphene oxide-IR780 hybrid nanosystems for effective cancer photothermal-photodynamic therapy

Publication . Melo, Bruna L.; Lima-Sousa, Rita; Alves, Cátia; Correia, I.J.; de Melo-Diogo, Duarte

Nanomaterials with near infrared light absorption can mediate an antitumoral photothermal-photodynamic response that is weakly affected by cancer cells’ resistance mechanisms. Such nanosystems are commonly prepared by loading photosensitizers into nanomaterials displaying photothermal capacity, followed by functionalization to achieve biological compatibility. However, the translation of these multifunctional nanomaterials has been limited by the fact that many of the photosensitizers are not responsive to near infrared light. Furthermore, the reliance on poly(ethylene glycol) for functionalizing the nanomaterials is also not ideal due to some immunogenicity reports. Herein, a novel photoeffective near infrared light-responsive nanosystem for cancer photothermal-photodynamic therapy was assembled. For such, dopamine-reduced graphene oxide was, for the first time, functionalized with sulfobetaine methacrylate-brushes, and then loaded with IR780 (IR780/SB/DOPA-rGO). This hybrid system revealed a nanometric size distribution, optimal surface charge and colloidal stability. The interaction of IR780/SB/DOPA-rGO with near infrared light prompted a temperature increase (photothermal effect) and production of singlet oxygen (photodynamic effect). In in vitro studies, the IR780/SB/DOPA-rGO per se did not elicit cytotoxicity (viability > 78 %). In contrast, the combination of IR780/SB/DOPA-rGO with near infrared light decreased breast cancer cells’ viability to just 21 %, at a very low nanomaterial dose, highlighting its potential for cancer photothermal-photodynamic therapy.

2023-10-23Journal article

Embargoed access

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

Publication . Lima-Sousa, Rita; Alves, Cátia; Melo, Bruna L.; Costa, Francisco J. P.; Nave, Micaela; Moreira, André F.; Mendonça, António; Correia, I.J.; de Melo-Diogo, Duarte

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.

2023-07-17Journal article

Embargoed access

Heptamethine Cyanine-Loaded Nanomaterials for Cancer Immuno-Photothermal/Photodynamic Therapy: A Review

Publication . Alves, Cátia; Sousa, Ana Rita Lima; Melo, Bruna L.; Moreira, André F.; Correia, I.J.; Diogo, Duarte de Melo

The development of strategies capable of eliminating metastasized cancer cells and preventing tumor recurrence is an exciting and extremely important area of research. In this regard, therapeutic approaches that explore the synergies between nanomaterial-mediated phototherapies and immunostimulants/immune checkpoint inhibitors have been yielding remarkable results in pre-clinical cancer models. These nanomaterials can accumulate in tumors and trigger, after irradiation of the primary tumor with near infrared light, a localized temperature increase and/or reactive oxygen species. These effects caused damage in cancer cells at the primary site and can also (i) relieve tumor hypoxia, (ii) release tumor-associated antigens and danger-associated molecular patterns, and (iii) induced a pro-inflammatory response. Such events will then synergize with the activity of immunostimulants and immune checkpoint inhibitors, paving the way for strong T cell responses against metastasized cancer cells and the creation of immune memory. Among the different nanomaterials aimed for cancer immuno-phototherapy, those incorporating near infrared-absorbing heptamethine cyanines (Indocyanine Green, IR775, IR780, IR797, IR820) have been showing promising results due to their multifunctionality, safety, and straightforward formulation. In this review, combined approaches based on phototherapies mediated by heptamethine cyanine-loaded nanomaterials and immunostimulants/immune checkpoint inhibitor actions are analyzed, focusing on their ability to modulate the action of the different immune system cells, eliminate metastasized cancer cells, and prevent tumor recurrence.

2022-05-08Journal article

Open access