MAGNETIC CARBON NANOSTRUCTURES AND STUDY OF THEIR TRANSPORT IN MICROFLUIDIC DEVICES FOR HYPERTHERMIA

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Magnetic carbon nanostructures and study of their transport in microfluidic devices for hyperthermia

Publication . Rodrigues, Raquel Oliveira; Lima, Rui A.; Gomes, Helder; Silva, Adrián

Cancer incidence and mortality are growing worldwide at an alarming pace, emphasizing the urgent need for new strategies to combat this disease. One of the frontiers of cancer research is currently focused on the design of multifunctional magnetic nanoparticles capable to achieve the synergistic cancer theranostics (both diagnosis and therapy). Although the potentiality that these multifunctional nanosystems represents to nanomedicine, cancer treatment and diagnostic, there are still many challenges that must be addressed in a near future before this approach became a reality. The development of efficient multifunctional magnetic nanosystems able to selectively destroy cancer cells in detriment of healthy ones, is one of the main challenges that have damped the spread of this technology into clinical applications. The limited biological and biophysical studies between the biomedical nanosystems and cells/tissues/organs is another challenge that has to be addressed. With these two main challenges in mind, the present Ph.D. work was focused in the development of: (1) Multifunctional magnetic carbon nanostructures as multifunctional nanosystems for the treatment of cancer, and (2) New advanced microfluidic devices capable to give new insights over the developed nanosystems and human cells.

2020Conference object

Open access

Multifunctional graphene-based magnetic nanocarriers for combined hyperthermia and dual stimuli-responsive drug delivery

Publication . Rodrigues, Raquel Oliveira; Baldi, Giovanni; Doumett, Saer; Garcia-Hevia, Lorena; Gallo, Juan; Bañobre-López, Manuel; Dražić, Goran; Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Lima, Rui A.; Gomes, Helder; Silva, Adrián

The synthesis of hydrophilic graphene-based yolk-shell magnetic nanoparticles functionalized with copolymer pluronic F-127 (GYSMNP@PF127) is herein reported to achieve an eﬃcient multifunctional biomedical system for mild hyperthermia and stimuli-responsive drug delivery. In vitro tests revealed the extraordinary ability of GYSMNP@PF127 to act as smart stimuli-responsive multifunctional nanomedicine platform for cancer therapy, exhibiting (i) an outstanding loading capacity of91% (w/w,representing 910μgmg−1) of the chemotherapeutic drug doxorubicin, (ii) a high heating eﬃciency under an alternating (AC) magnetic ﬁeld (intrinsic power loss ranging from 2.1–2.7nHm2kg−1), and (iii) a dual pH and thermal stimuli-responsive drug controlled release (46% at acidic tumour pH vs 7% at physiological pH) under AC magnetic ﬁeld, in just 30min. Additionally, GYSMNP@PF127 presents optimal hydrodynamic diameter (DH=180nm) with negative surface charge, high haemocompatibility for blood stream applications and tumour cellular uptake of drug nanocarriers. Due to its physicochemical, magnetic and biocompatibility properties, the developed graphene-based magnetic nanocarrier shows high promise as dual exogenous (AC ﬁeld)/endogenous (pH) stimuli-responsive actuators for targeted thermo-chemotherapy, combining magnetic hyperthermia and controlled drug release triggered by the abnormal tumour environment. The presented strategy and ﬁndings can represent a new way to design and develop highly stable added-value graphene-based nanostructures for the combined treatment of cancer.

2018Journal article

Open access

Wall expansion assessment of an intracranial aneurysm model by a 3D digital image correlation system measurement

Publication . Rodrigues, Raquel Oliveira; Pinho, Diana; Bento, David; Lima, Rui A.; Ribeiro, J.E.

Intracranial aneurysm is a local dilatation of an intracranial artery with high risk of rupture and death. Although it is generally accepted that the weakening of the arterial wall is the main cause for the rupture of an aneurysm, it still no consensus about the reasons for its creation, expansion and rupture. In particular, what is the role played by the blood flow in these phenomena. In this way, the aim of this work is the in vitro mechanical assessment of the wall expansion, namely the displacements, deformations and strains occurring in a saccular intracranial aneurysm model, when subjected to different flow rates. To obtain new insights into the mechanisms involved in the aneurysm rupture, a 3D-VicTM Digital Image Correlation System was used and validated with a finite element analysis. The wall expansion results have revealed that the displacements, deformations and principal strains are directly related to the internal pressure caused by the fluid on the wall of the aneurism. These findings were especially observed in the weakened areas of the aneurysm model, where the wall was thinner. Furthermore, the technique used in this study has shown to be a potential method to validate numerical simulations of aneurysms, allowing the future performance of more complex and realistic haemodynamic studies.

2016Journal article

Restricted access

A Tailor-made protocol to synthesize yolk-shell graphene-based magnetic nanoparticles for nanomedicine

Publication . Rodrigues, Raquel Oliveira; Baldi, Giovanni; Doumett, Saer; Gallo, Juan; Bañobre-López, Manuel; Dražić, Goran; Calhelha, Ricardo C.; Ferreira, Isabel C.F.R.; Lima, Rui A.; Silva, Adrián; Gomes, Helder

A simple tailor-made protocol to synthesize graphene-based magnetic nanoparticles (GbMNPs) for nanomedicine is herein reported. Different GbMNPs with very distinctive physicochemical and toxicological properties were synthesized by adjusting the number of carbon precursors in the coating of superparamagnetic iron oxide nanoparticles. In vitro tests show the ability to use these GbMNPs as intelligent and on-demand drug nanocarrier systems for drug delivery, exhibiting the following features: good colloidal stability, good loading capacity of the chemotherapeutic drug doxorubicin, high pH-controlled release of the encapsulated drug (targeting tumour acidic pH conditions), superparamagnetic behaviour and biocompatibility. Due to their combined properties (i.e., physicochemical, magnetic, and biocompatibility), GbMNPs show high potentiality to be combined with other biomedical techniques, such as magnetic hyperthermia, which can represent an enhancement in the treatment of cancer.

2018Journal article

Open access

Low cost microfluidic device for partial cell separation: micromilling approach

Publication . Lopes, Raquel; Rodrigues, Raquel Oliveira; Pinho, Diana; Valdemar, Garcia; Schütte, Helmut; Lima, Rui A.; Gassmann, Stefan

Several studies have already demonstrated that it is possible to perform blood flow studies in microfluidic systems fabricated by using low-cost techniques. However, most of these techniques do not produce microchannels smaller than 100 microns and as a result they have several limitations related to blood cell separation. Recently, manufacturers have been able to produce milling tools smaller than 100 microns, which consequently have promoted the ability of micromilling machines to fabricate microfluidic devices able to perform separation of red blood cells (RBCs) from plasma. In this work, we show the ability of a micromilling machine to manufacture microchannels with dimensions down to 30 microns. Additionally, we show for the first time the ability of the proposed microfluidic device to enhance the cell-free layer close to the walls, leading to perform partial separation of RBCs from plasma.

2015Conference object

Open access