Development of a responsive multi-layer microneedle patch for the sequential PTT/PDT and immunotherapy of invasive breast cancer

Funder

Organizational Unit

Publications

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

IR780 loaded sulfobetaine methacrylate-functionalized albumin nanoparticles aimed for enhanced breast cancer phototherapy

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

New insights about nanomaterials' biodistribution revealed their ability to achieve tumor accumulation by taking advantage from the dynamic vents occurring in tumor's vasculature. This paradigm-shift emphasizes the importance of extending nanomaterials' blood circulation time to enhance their tumor uptake. The classic strategy to improve nanomaterials' stability during circulation relies on their functionalization with poly(ethylene glycol). However, recent reports have been showing that PEGylated nanomaterials can suffer from the accelerated blood clearance phenomenon, emphasizing the importance of developing novel coatings for functionalizing the nanomaterials. To address this limitation, the modification of natural carriers' surface to enhance their stability appears to be a promising strategy. Herein, sulfobetaine methacrylate (SBMA)-functionalized bovine serum albumin (BSA) was synthesized for the first time to investigate the capacity of this modification to improve the resulting nanoparticles' physicochemical properties, colloidal stability and in vitro performance. This novel polymer was then employed in the formulation of nanoparticles loaded with IR780 for application in breast cancer phototherapy (IR/SBMA-BSA NPs). When compared to their non-functionalized equivalents, the IR/SBMA-BSA NPs presented a neutral surface charge and a higher stability in biologically relevant media. Due to these features, the IR/SBMA-BSA NPs could achieve a 1.9-fold greater uptake by breast cancer cells than IR/BSA NPs. Furthermore, the IR/SBMA-BSA NPs were cytocompatible towards normal cells and reduced breast cancer cells' viability up to 42%. The phototherapy mediated by IR/SBMA-BSA NPs could further decrease cancer cells' viability to about 12%. Overall, the IR/SBMA-BSA NPs have enhanced features that propel their application in breast cancer phototherapy.

2020-04-18Journal article

Open access

Injectable in situ forming hydrogels incorporating dual-nanoparticles for chemo- photothermal therapy of breast cancer cells

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

Chemo-photothermal therapy (chemo-PTT) mediated by nanomaterials holds a great potential for cancer treatment. However, the tumor uptake of the systemically administered nanomaterials was recently found to be below 1 %. To address this limitation, the development of injectable tridimensional polymeric matrices capable of delivering nanomaterials directly into the tumor site appears to be a promising approach. In this work, an injectable in situ forming ionotropically crosslinked chitosan-based hydrogel co-incorporating IR780 loaded nanoparticles (IR/BPN) and Doxorubicin (DOX) loaded nanoparticles (DOX/TPN) was developed for application in breast cancer chemo-PTT. The produced hydrogels (IR/BPN@Gel and IR/BPN+DOX/TPN@Gel) displayed suitable physicochemical properties and produced a temperature increase of about 9.1 °C upon exposure to Near Infrared (NIR) light. As importantly, the NIR-light exposure also increased the release of DOX from the hydrogel by 1.7-times. In the in vitro studies, the combination of IR/BPN@Gel with NIR light (photothermal therapy) led to a reduction in the viability of breast cancer cells to 35 %. On the other hand, the non-irradiated IR/BPN+DOX/TPN@Gel (chemotherapy) only diminished cancer cells' viability to 85 %. In contrast, the combined action of IR/BPN+DOX/TPN@Gel and NIR light reduced cancer cells' viability to about 9 %, demonstrating its potential for breast cancer chemo-PTT

2021-03-17Journal article

Open access

Sulfobetaine methacrylate-albumin-coated graphene oxide incorporating IR780 for enhanced breast cancer phototherapy

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

Aim: Enhance the colloidal stability and photothermal capacity of graphene oxide (GO) by functionalizing it with sulfobetaine methacrylate (SBMA)-grafted bovine serum albumin (BSA; i.e., SBMA-g-BSA) and by loading IR780, respectively. Materials & methods: SBMA-g-BSA coating and IR780 loading into GO was achieved through a simple sonication process. Results: SBMA-g-BSA-functionalized GO (SBMA-BSA/GO) presented an adequate size distribution and cytocompatibility. When in contact with biologically relevant media, the size of the SBMA-BSA/GO only increased by 8%. By loading IR780 into SBMA-BSA/GO, its photothermal capacity increased by twofold. The combination of near infrared light with SBMA-BSA/GO did not induce photocytotoxicity on breast cancer cells. In contrast, the interaction of IR780-loaded SBMA-BSA/GO with near infrared light caused the ablation of cancer cells. Conclusion: IR780-loaded SBMA-BSA/GO displayed an improved colloidal stability and phototherapeutic capacity.

2021-03-04Journal article

Open access

Sulfobetaine methacrylate-functionalized graphene oxide-IR780 nanohybrids aimed at improving breast cancer phototherapy

Publication . Leitão, Miguel; Alves, Cátia; Diogo, Duarte de Melo; Sousa, Rita Lima; Moreira, André F.; Correia, I.J.

The application of Graphene Oxide (GO) in cancer photothermal therapy is hindered by its lack of colloidal stability in biologically relevant media and modest Near Infrared (NIR) absorption. In this regard, the colloidal stability of GO has been improved by functionalizing its surface with poly(ethylene glycol) (PEG), which may not be optimal due to the recent reports on PEG immunogenicity. On the other hand, the chemical reduction of GO using hydrazine hydrate has been applied to enhance its photothermal capacity, despite decreasing its cytocompatibility. In this work GO was functionalized with an amphiphilic polymer containing [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA) brushes and was loaded with IR780, for the first time, aiming to improve its colloidal stability and phototherapeutic capacity. The attained results revealed that the SBMA-functionalized GO displays a suitable size distribution, neutral surface charge and adequate cytocompatibility. Furthermore, the SBMA-functionalized GO exhibited an improved colloidal stability in biologically relevant media, while its non-SBMA functionalized equivalent promptly precipitated under the same conditions. By loading IR780 into the SBMA-functionalized GO, its NIR absorption increased by 2.7-fold, leading to a 1.2 times higher photothermal heating. In in vitro cell studies, the combination of SBMA-functionalized GO with NIR light only reduced breast cancer cells' viability to 73%. In stark contrast, by combining IR780 loaded SBMA-functionalized GO and NIR radiation, the cancer cells' viability decreased to 20%, hence confirming the potential of this nanomaterial for cancer photothermal therapy.

2020-10-14Journal article

Open access