Project Portugal 2030

Summary

Over the past decade, several diseases, including cancer, blood clots, and intestinal infections, have surfaced as significant threats to human health. Although advancements in medicine have led to the development of new pharmaceutical agents targeting these conditions, their effectiveness in penetrating and distributing within affected tissues remains limited. Advancements in nanotechnology, combining experts in physics, chemistry, and biology, have been applied to the field of medicine creating a myriad of different nanoparticles aimed at enhancing the efficacy of current treatments. Still, the clinical translation of nanodevices for the treatment and detection of cancer has been strongly impaired due to the lack of understanding of the nanoparticle delivery mechanisms to solid tumors. Physical and biological barriers such as flow diffusion, protein adsorption, phagocytic uptake, and renal clearance, impact the amount of particles reaching the targeted tissue. Moreover, tumor heterogeneity, ECM composition, and high interstitial fluid pressure due to abnormal vasculature hinder uniform drug distribution, compromising the overall effectiveness of the treatment. Recently, nanotechnology and microfabrication approaches have been combined to develop a new class of devices called nano-to-micro robots, tailored for personalized and precision applications in therapeutics, diagnosis, drug delivery, and surgery. The terminology of these innovative devices relies on their ability to be externally controlled by magnetic forces, light, or ultrasound. Challenges associated with most of these devices include poor cost-effective scalability, difficulties in visually tracking the devices, and insufficient relevant data on biocompatibility. To face these challenges, we propose the development of groundbreaking miniaturized magneto-enzymatic devices (MEMD) using biocompatible materials (superparamagnetic iron oxide nanoparticles, gelatin, and hyaluronidase) and external stimuli (magnetic field and NIR light), for deep cancer therapy. By taking advantage of the solid tumor ECM composition, we aim to develop a complementary enzymatic device capable of deeply penetrating the tumor, based on the interplay between the enzymatic activity and external magnetic force. Also, this MEMD will be designed to serve a dual role as a drug delivery vehicle and a PTT agent. Ideally, upon reaching the targeted site, NIR light will activate the MEMD, increasing tissue temperature and triggering the release of encapsulated API. This dual action aims to facilitate drug penetration into deeper regions and sensitize cancer cells to chemotherapy effects, overcoming the limitation of individual-based therapies. Glioblastoma (GBM), a highly aggressive tumor to which chemotherapy inefficacy is attributed to limited drug diffusion through the blood-brain barrier, will serve as a proof-of-concept to assess the effectiveness of our MEMD to target tumors from nearby tissue regions. Natural-derived hydrogels containing 3D GMB spheroids will be used to mimic the tumor microenvironment more accurately, replicating cellular function and MEMD penetration into this biomimetic 3D model. In the future, neurosurgeons will apply the device through minimally invasive procedures to more accessible areas, then guide it precisely to the less accessible target area with the aid of a finely tuned external magnetic field and MRI imaging technologies, ensuring minimal interference with healthy tissue.