Triple-negative breast cancer (TNBC) represents 20% of the 3 million breast cancers diagnosed in women worldwide every year. In Portugal, the incidence of breast cancer is 118.5 women per 100000 population, which represents 30% of the newly diagnosed cancer cases in women every year and continues to show a high mortality rate.

The only systemic therapy currently available for patients with TNBC is (neo)adjuvant therapy with various cytotoxic chemotherapeutic agents. However, the lack of targeted therapeutic options, together with the limited efficacy of current treatments as well as the adverse effects associated with them, demands an urgent effort to develop novel targeted therapies and early diagnostic methods. Triple-negative breast cancer (TNBC) is often among the highest-grade and poorer prognosis breast cancers, mainly because targeted therapy is not available. Therefore, there is an urgent demand to discover specific targets and develop novel targeted therapies as well as early diagnostic methods.

The main objective of this project was to ameliorate the prognosis of TNBC through the preparation and preclinical validation (in vitro plus in vivo) of a targeted theranostic nanoparticle/probe that is able to specifically recognize tumor-associated macrophages (TAMs), offering a non- invasive imaging capability by MRI together with a synergic magnetic hyperthermia (MH)and chemotherapy treatment against TNBC. This initiative represents an innovative and ground-breaking use of tailored hybrid nanocomposites as an innovative and tangible solution in the field of targeted drug delivery against cancer, TNBC in particular. The lack of targeted therapeutic options against TNBC, the limited efficacy of current treatments and the well-known secondary effects of conventional chemotherapeutic treatments open the gate to develop novel targeted therapies as well as early diagnostic methods. Imaging and externally controlled drug delivery capabilities, in combination with magnetic hyperthermia and active targeting, will be integrated into one single platform.

The expected scientific advances will contribute to the ultimate clinical translation and a wide-range of innovations with potential to impact the triple-negative breast cancer therapy, being also a step forward on the way to targeted, image-guided therapies of cancer. To the best of the team’s knowledge, there is no one single theranostic nanomedicine that made it into the clinics. Also, the clinical translation of developed controlled drug delivery systems is very limited and just a few examples can be found in the market, which is fully dominated by the small molecule drugs. Thus, the combination of a not yet existing market of ‘theranostic medicines’ (estimated in 20 bn) and that of controlled drug delivery (70bn) constitutes a new medical framework and market opportunity for specific theranostic systems with proved targeted, imaging and therapeutic efficiencies.