In the ULISES project, we aim at developing an immunologic-based treatment strategy where cancer cells are “reprogrammed” to become “visible” to the patient’s own immune system, which will see them as “not belonging to the body” and will attack them, emulating the allogenic response to incompatible transplants. Thus, it will constitute a “natural” treatment, as the patient’s own immune system will be used to attack cancer cells, with no drugs, chemotherapy, radiotherapy, transplants, etc., significantly reducing the treatment time to few weeks and producing minimal or almost null side effects. In addition, this “reprogramming” will lead to an “immunological-memory” avoiding future relapses (vaccine-like effect) through TIL (Tumour Infiltrating Lymphocytes) generated around the tumour microenvironment by the immune system. Porous nanoparticles (NPs) will be used as carriers for delivering a plasmid DNA cargo into the tumour cells in order to produce that “reprogramming”. These NPs will specifically recognize the cancer cells through the CD47 protein and the folate receptors beta and alpha, highly expressed on the surface of the cells. Moreover, two messenger RNAs will be used in order to avoid the side effects caused by targeting CD47 protein (mainly anaemia, neutropenia and thrombocytopenia). Finally, highlight that the ULISES therapeutic strategy will be a “global” treatment, since only with 3 subtypes of NP (one for each chosen alloHLA-A), we will be able to target the entire population for each cancer type. For the implementation and validation of this strategy, we will focus on pancreatic cancer because of its high aggressiveness, lack of effective treatments and little life expectancy, but the developed strategy will also be valid for other cancer varieties with minimal modifications.

The SAPHELY project focuses on the development and the preclinical validation of a nanophotonic-based handheld point-of-care (POC) analysis device for its application to the minimally-invasive early diagnosis of diseases, with a focus in cancer. Disease identification will be based in the fast (<5 minutes), ultra-sensitive (sub-pM) and label-free detection of novel highly-specific microRNA (miRNA) biomarkers, using a small volume of whole blood (<100 μL). This POC analysis device, which will have a low cost (envisaged cost < €3000), will significantly help in the implementation of mass screening programs, with the consequent impact on clinical management, reducing also costs of treatments, and increasing survival rates. The ultra-high sensitivity required for the direct detection of miRNA biomarkers present in the bloodstream will be achieved by using a novel sensing amplification technique. This technique is based in the use of molecular beacon capture probes with an attached high index nanoparticle, so that the hybridization events are translated into the displacement of these nanoparticles from the sensor surface. The use of this self-amplification technique avoids the use of complex PCR-based amplification methods or labelling processes, which are difficult to implement on-chip. The cost, size and weight reduction required for deploying an affordable handheld POC device will be achieved by using a novel power-based readout scheme for photonic bandgap sensing structures where the use of expensive, bulky and heavy tuneable lasers and spectrometers is avoided. Special attention will be paid within the SAPHELY project to explore the potential deployment and commercialisation of the analysis device, by means of the involvement of relevant academic and industrial partners, as well as end users.

DISRUPT aims at revolutionising the field of biomedical imaging by developing a radically new lab-a-on-chip technology: integrated tomographic microscopy. This unprecedented technique will be enabled by pushing forward the science of on-chip wireless photonics and tomography, in combination with microfluidics and artificial intelligence (AI). The CMOS compatibility of this technology represents a paradigm shift as it assures the realization of tomographic microscopes that are dramatically cheaper, lighter, and smaller than current approaches. Moreover, the singular features of the proposed solution introduce key advantages in terms of resolution, sensitivity, throughput, parallelisation, and energy efficiency. To illustrate its potential, we will show that on-chip TPM can be used for cancer detection and the identification of infected cells. Developments related to fundamental nanoantenna and diffraction tomography science, nanophotonics, nanofabrication, microfluidics, AI and clinical validation will be undertaken by a consortium comprised by 2 SME, 1 HE, 1 Non-profit RO and 2 Cancer R&D Medical institutions, with complementary expertise, leaders in their respective markets and R&D fields. This novel device is suited for many applications, such as early cancer diagnosis, cell characterisation, research on cancer and infectious diseases, immunocyte phenotyping, stem cell multipotency identification, tissue pathology, haematopathology, and analysis of infected cells. Its intrinsic mass-producible, compact, low-cost, mechanically robust, and energy-efficient feature makes this technology a future innovation driver for new developments in many biomedical application fields, and offers an alternative toolset addressing some of the emerging needs of microscopic analysis and diagnostics in low-resource settings, telemedicine applications and point-of-care, having a potentially huge societal impact fostering early diagnosis of cancer and other diseases and infections.