Angela Privat Maldonado

Research Angela Privat Maldonado

Research team

Expertise

Application of low-temperature plasmas for cancer research using 3-dimensional in vitro models and in ovo TUM-CAM model Study of the effect of plasma-generated reactive species in the tumor microenvironment, pancreatic cancer cells and stellate cells, with specific emphasis on the role of stellate cells in the migration of cancer cells upon treatment Live imaging of 3D spheroids, assessment of viability, cell death. Analysis of proliferative markers, extracellular matrix components, hypoxia by immunohistochemistry / immunofluorescence Multi-arrays for 3~D spheroids in paraffin, cryosectioning

Effect of non-thermal plasma in cancer treatment: Investigating the modulation of cell-to-cell communication via gap junctions in the tumour microenvironment. 01/01/2024 - 31/12/2027

Abstract

Despite the progress made on therapeutic strategies for cancer, the development of resistance is the most important challenge. A novel approach for cancer treatment is the induction of cell death by oxidative stress upon increasing the reactive oxygen and nitrogen species (RONS) levels in cancer cells. Non?thermal plasma (NTP) is a promising novel therapy based on the localized delivery of RONS, and it has strong anti-cancer effects in multiple cancer types. NTP can affect cell communication between cancer cells via specialized structures, called gap junctions (GJs). GJs can transport molecules (including death signals and RONS) between cells. However, normal cells of the tumour microenvironment (TME) can rescue cancer cells from cell death and promote resistance via GJs. To date, little is known about how NTP changes GJ cell communication in the TME. We aim to determine how NTP treatment affects GJ communication between cancer and other cells of the TME (such as stromal and endothelial cells). We will combine computer simulations and experimental work using well-established pancreatic ductal adenocarcinoma models. We will evaluate NTP effects on 2D, 3D, and in ovo cancer models, next to in silico analysis. Altogether, this will significantly advance our understanding of the mechanisms of action of NTP for cancer, in novel models that consider the role of other TME cells in the response and will allow the development of better therapies.

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  • Research Project

Inducing angiogenesis in pancreatic cancer with cold atmospheric plasma to enhance drug delivery and efficacy. 01/11/2021 - 31/10/2025

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with five-year survival rates of 2-9% and is predicted to become the third leading cause of cancer death in the EU by 2025. PDAC tumors show hypovascularity and vascular compression, causing chemoresistance, resulting from desmoplasia by pancreatic stellate cells (PSCs). Evidence has shown that a pro-angiogenic approach for PDAC increases drug delivery and efficacy, reducing tumor growth and metastasis. Cold atmospheric plasma (CAP) treatment is a novel and safe technology known to induce angiogenesis at low treatment doses. The objective and novelty of my project is to use mild CAP treatment to enhance the delivery and effect of chemotherapeutic drugs by inducing angiogenesis for a synergistic anti-cancer effect. The kINPen® plasma jet will be used to determine optimal CAP treatment conditions. Spheroid co-cultures of pancreatic cancer cells, PSCs and endothelial cells will be investigated. Gemcitabine will be used as chemotherapeutic drug and administration to 3D spheroids will be performed with the novel OrganoPlate® Graft, which allows vascularization of 3D in vitro models and increases the predictive power of in vitro work. Clinical efficacy will be evaluated by combining distal pancreatectomy with intra-operative CAP treatment and adjuvant chemotherapy in an orthotopic mouse model. This project will lead to a novel combinational treatment strategy for PDAC patients that can have partial or full resection.

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  • Research Project

Development of a plasma device for rapid disinfection of contaminated hospital materials: Hospital‐Use Plasma Unit (HUP‐Unit). 01/09/2022 - 31/08/2023

Abstract

The SARS‐CoV‐2 pandemic has exposed how unprepared our society was in preventing the propagation of highly infectious diseases, protecting the healthcare providers and patients, and efficiently organizing the logistics, while managing large numbers of patients. For the past two years, hospitals have battled to mitigate the spread of the virus in their facilities, a challenge that included the need to daily dispose of thousands of unused, individually‐packaged medical products that could not be disinfected with the traditional disinfection methods. On average, the Antwerp University Hospital (UZA) produced around 250,000 kg of medical waste per year. In 2021, the amounts of medical waste increased by more than 10% compared to the pre‐COVID period. Globally, the pandemic not only increased the cost for hospitals, but it also increased the generation of waste around the world by 400‐500%. Moreover, at the height of the pandemic, there was even a critical shortage of medical supplies. Therefore, this was not only an environmental and financial issue, but also a serious healthcare burden. In order to be better prepared for future pandemics, we have prepared a mission‐oriented innovation project, which responds to a specific request from the Intensive Care Unit (ICU) at UZA. In our IOF‐POC CREATE project here, we aim to develop a non‐thermal plasma (NTP)‐based disinfection device to rapidly eliminate viruses from unused, individually‐packaged medical products: the hospital‐use plasma unit (HUP‐unit). Our HUP‐device will utilize a completely innovative cylindrical geometry design feature with materials to be disinfected, to enhance NTP generation and contact with a large volume of material, and ensure complete, uniform treatment. Indeed, we have to design a completely novel NTP device concept, which we will categorize as a 'moving‐bed' dielectric barrier discharge (DBD). By using the individually‐packaged hospital products as part of the NTP generation mechanism, our 'moving‐bed' DBD HUP‐unit offers a scalable solution to provide rapid disinfection in the hospital. Based on our understanding of plasma dynamics and computational plasma simulations, we have developed this theoretical design, but the feasibility of creating a working prototype remains to be seen. Therefore, in this IOF‐POC CREATE project, we will produce and validate our prototype HUP‐unit in the lab. If successful, our HUP‐unit will allow us to: i) mitigate shortages in individually‐packaged medical products; ii) reduce the waste produced by healthcare facilities and associated waste management cost; iii) reduce the incidence of hospital‐acquired infections.

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Project type(s)

  • Research Project