Ongoing projects:
UnTAM
Unleashing the tumour associated macrophage (TAM) workforce to fight against cancer from the inside
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Tumor-associated macrophages (TAMs) constitute as much as 50% of the mass in certain tumour tissues. New trends in the field of cancer treatment are starting to consider this particular type of cells as a therapeutic target, particularly in tumor subtypes where other targets are not available (a good example is triple-negative breast cancer, TNBC). However, it is still an open question whether TAMs can be safely utilized as a therapeutic target. Macrophages in general can be polarized into M1 or M2 phenotypes by their local environment. While M1 macrophages present bactericidal, pro-inflammatory and immunostimulatory activities, M2 phenotype promote tissue repair, angiogenesis, matrix remodeling and immunosuppression. Overall, M1 type TAMs are considered to present anti-tumor activity while M2 are regarded as pro-tumoral. Unfortunately, TAMs are largely polarized into the M2 phenotype, giving support to the growth and metastasis of the tumor mass. Thus, a depletion of TAMs via a targeted strategy would have a dual positive effect on tumor progression, i) tumor burden would be greatly reduced and ii) the local immunosuppressive environment of the tumor would be (to some extend) relieved. A number of strategies have been proposed and tested in this direction. Here we propose to go a step further and instead of targeting TAMs aiming at their depletion, we hypothesize that these large colony of macrophages already in the tumour site can be reprogrammed into M1 anti-tumor macrophages and they can be unleashed to lead the attack against cancer from the inside. In order for this strategy to be successful, the reprogramming of TAMs must take place at a local level, because the systemic activation of M1 macrophages would have dramatic consequences. To achieve this specific M1 TAM polarization we propose to combine a TAM targeted drug delivery system (DDS) to deliver immunostimulating drugs, with local external triggering of the drug release. On top of this, a longitudinal monitoring of the response-to-treatment will be implemented through non-invasive magnetic resonance imaging(MRI).
BrainChip4MED
Brain-on-a-chip as a preclinical model tool for the screening of theranostic nanoformulations for neurodegenerative diseases
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Current neurological and neurodegenerative diseases treatments are limited and ineffective. This is mainly due to the complexity of the brain and the inability of most drugs to cross the blood–brain barrier. The EU-funded BrainChip4MED project hosted by AmThema group at INL (Portugal) with a secondment at Harvard Medical School/Brigham Women’s Hospital (USA), aims to develop an in vitro model for studying brain-targeting nanocarriers as drug vehicles to the brain. Researchers will employ brain-on-a-chip (BoC) technology to generate a microfluidic-based model and combine it with multiplex biosensors to screen various nanoformulations in real-time. The project will also be focused on the development of novel brain-targeting nanoformulations, which can lead to the treatment of Alzheimer’s disease.
PROMISEANG
alternative PROteins from MIcrobial fermentation of non-conventional SEA sources for Next-Generation food, feed and non-food bio-based applications
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PROMISEANG aims to develop novel proteins from underexploited marine sources, including marine invertebrate and macroalgae discards and industrial biowaste and by-products, through fermentation using fungi, yeast or bacteria. This should generate new microbial protein biomass that meets market requirements for food, animal feed and non-food products such as pharmaceuticals and cosmetics.
A technically and economically viable biorefinery for microbial-based protein production will be demonstrated, allowing for high yields, reduced production times and costs, minimal environmental impact and increased availability of proteins in the EU. Taking a zero-waste approach, PROMISEANG will also recover and synthesise non-protein bio-compounds and molecules for food, feed and non-food applications.
Successfully completed projects:
In Portugal, the incidence of breast cancer represents 30% of the new diagnosed cancer cases in women every year, with mortality indexes of 18%. Among them, 20% corresponds to triple-negative breast-cancer (TNBC), the most lethal stripe. TNBC lacks the expression of any of the most common receptors and growth factors used for the clinical diagnosis of breast cancers. The only systemic therapy currently available for patients with TNBC is adjuvant chemotherapy with various combinations of anthracyclines , taxanes or cyclophosphamide. However, the response to the treatment is far from ideal. High rates of relapse, in addition to low survival rates in patients with residual disease after treatment, are observed. Therefore, the lack of targeted therapeutic options, the limited efficacy of current treatments, together with the well-known harmful side effects of chemotherapy, demand an urgent effort to discover specific targeting strategies that enable early diagnostic methods and on-site therapies.
The main objective of this project is to ameliorate the prognosis of TNBC through the preparation and validation of a biocompatible target-less theranostic probe able to offer active accumulation on tumor site under external stimuli, non-invasive imaging capabilities and combinatorial therapy. To achieve this ambitious goal, solid lipid nanoparticles (SLNs) will be synthesized from commercially available sources, simultaneously loaded with a cocktail of drugs and nanoparticles, and surface functionalized with different responsive ligands.
Overall, at the end of the project an in vitro and in vivo validated theranostic probe will be delivered showing i) active targeting, ii) combinatorial therapy, and iii) T2w-MR imaging capabilities. These expected results will enable translational research and will be key in the advance towards an adequate and timely therapeutic intervention in patients with TNBC, being also a step forward on the way to targeted image-guided therapies of cancer.
Cancer is one of the deadliest threats to mankind in the 21st century. Colorectal cancer in particular is the 3rd most common cancer type in Portugal and represents a serious health problem in the northern regions of the country. This proposal aims to have a positive impact on the prognosis of CRC through an alternative treatment scheme combining local immunostimulation and hyperthermia, plus an optimized decision making protocol based on real-time early treatment response monitoring.
This project proposes the preparation, characterization and in vitro validation of a drug delivery system comprising an inorganic core plus a polymeric coating. The presence of these two components responds to different needs. The inorganic core plays a dual role; on one hand it enables the longitudinal non-invasive detection and tracking of the system via biomedical imaging techniques, while on the other it will be used as external effector to trigger drug release. The second component of the system, the polymer, will be used to encapsulate and, more importantly, release on-demand a cocktail of drugs. A combination of release mechanisms limits the exposure of healthy tissues to the drugs and potentiates the therapeutic effect on the tumour. Together with these responsive drug delivery capabilities, the proposed drug delivery nanocomposite will be equipped with a reporting system for the real-time evaluation of treatment response that will enable the implementation of an early check-point to evaluate the efficacy of the treatment.
2IQbio neuro
Chemical Biology focuses on the design and synthesis of chemical tools to be used as probes for the study and rational modification of biological processes. One of the greatest challenges in science is to obtain laboratory compounds that act in a predetermined way once inside biological systems (cells, animal models, clinical trials), to develop new therapies and diagnostic methodologies. 2IQbioneuro manages a network in research and innovation in Chemical Biology for the treatment of neurological diseases associated to aging.
SAFE-N-MEDTECH
SAFE-N-MEDTECH, Safety testing in the life cycle of nanotechnology-enabled medical technologies for health
Society and clinical practice pose a growing demand on novel biomaterials, ICT, micro and nanotechnologies for innovative medical devices and in vitro diagnostics (Medical Technologies-MTs). In addition to the challenge of time, the new technologies are subjected to other pressing factors such as qualification, regulation, cost, biocompatibility and the need to be applicable worldwide. In the most recent years it is obvious that nano-enabled MTs can be applied in nearly every medical area, with a major presence and increased importance in cancer, regenerative medicine, advanced therapies, neurology, cardiology, orthopaedics, and dentistry. On the other hand, any innovation in the Health sector has to be carefully assessed in terms of risk/benefit ratio. Nano-enabled MTs particularly require careful assessment, since they are complex products group and their technological assessments are still under development. This assessment will be a key pillar for the here proposed Open Innovation Test Bed (OITB)
To address all the aforementioned challenges, the SAFE-N-MEDTECH consortium aims to bring a strong and competitive cooperation to compete in the market for a coordinated OITB for nano-enabled MTs. SAFE-N-MEDTECH will build an innovative open access platform to offer to companies and reference laboratories, the capabilities, knowhow, networks and services required for the development, testing, assessment, upscaling and market exploitation of nanotechnology-based Medical and Diagnosis Devices. This across the whole Life Cycle. This OITB will offer a multidisciplinary and market oriented innovation approach to SME´s, Healthcare providers and Industries for the translation to the market of MTs, based on a deep understanding and knowledge of the material-nanoproperties, their advance use and applications in MTs and other aspects involved in MTs safety (electric compatibility, electromagnetic properties, etc).
PANA, Promoting active ageing: functional nanostructures for Alzheimer's disease at ultra-early stages.
Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. Progressive aging of EU population will increase the magnitude of this problem in the next decades. To date, no effective method for the early diagnosis or the treatment of AD exists. Therefore, there is an urgent need to develop new early diagnostic and therapeutic strategies to delay and revert the appearance of the most adverse symptoms of this disease. PANA project will be based on two fundamental pillars; on one hand, efforts will be focused on multimodal PET/MRI imaging which is gaining relevance as the best solution for diagnostic purposes due to the complementary advantages of both technologies, combining the high structural characterization of tissue provided by MRI with the enhanced sensitivity of PET imaging. On the other hand, theranostic nanostructures will be developed to provide in situ diagnostic and therapeutic effects. Therefore, PANA project focuses on the development of theranostic nanostructures that specifically recognize very-early molecular markers of AD, can be detected by means of non-invasive and already available imaging methodologies, and that will provide a therapeutic action if needed. To achieve this goal, we propose a unique consortium which combines neuroscientists, nanotechnologists, molecular imaging experts, clinicians and Small/Medium/Large Enterprises in an effort to use smart nanoparticles engineered with multifunctional biomaterials to provide a new diagnostic/therapeutic tool for AD, a vital medical/social problem in EU.
NANOTHER
NANOTHER, TAMs-targeted and externally controlled nanotheranostics of triple-negative-breast-cancer.
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Triple-negative-breast-cancer (TNBC) represents 20% of the 3 million breast cancer tumors diagnosed in women worldwide every year. The lack of targeted therapeutic options, the limited efficacy of current treatments, together with the harmful side effects of chemotherapy, highlight the real need for the development novel drug nanocarriers and new strategies for the diagnosis and treatment of the disease.
Due to the lack of specific receptors in TNBC, cellular biomarkers have been particularly pursued. In particular, tumor associated macrophages (TAMs) are becoming main actors in imaging and therapeutic efforts.
The main objective of this project is to ameliorate the prognosis of TNBC through the preparation and preclinical validation up to small animal models of a targeted theranostic probe able to specifically recognize and accumulate on TAMs, offering non-invasive imaging capabilities and a synergistic combinatorial treatment.
MAGNETIC NANOCOMPOSITE HYDROGELS FROM BIOPOLYMERS AS SMART DELIVERY SYSTEMS
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The present project aims at designing, synthesizing and formulating novel nanocomposite smart hydrogels from a range of natural polymers for applications as remotely controlled delivery systems. It will create know-how on the rational use of natural resources in this particular field of nanotechnology to develop products with an added value, yet cost effective, that can have an impact in societal challenges related to human health. Particularly, this proposal will build up on the expertise of participating teams in the areas of biopolymers and nanomaterials and will contribute to foster collaboration and increase consolidation in those particular areas of research.
1- SYNTHESIS AND CHARACTERIZATION OF MAGNETIC NANOSYSTEMS ASSOCIATED TO CO-POLYMERS AND POLYSACCHARIDESFOR A CONTROLLED DRUG DELIVERY
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2-PREPARATION AND CHARACTERIZATION OF MAGNETIC NANOPARTICLES FOR HEALTH AND ENVIRONMENTAL APPLICATIONS
