NanoTher:
TAMs-targeted and externally controlled nanotheranostics of triple-negative-breast-cancer.
.png)
Project aim:
Triple Negative Breast Cancer (TNBC) represents 20% of the 3 million breast cancer cases diagnosed every year worldwide. In Portugal, the incidence of breast cancer is of 118.5 cases per 100,000 population (2010 data, Registro oncológico nacional), which represents 30% of the new diagnosed cancer cases in women every year, and still shows mortality indexes of 18%. TNBC is a particular subtype of breast cancer that lacks the expression of any of the most common receptors and growth factors used for the clinical diagnosis of breast cancer, namely ER, PR and HER2. The only systemic therapy currently available for TNBC patients is adjuvant chemotherapy with various combinations of anthracyclines (e.g. doxorubicin), taxanes (e,g, paclitaxel), or cyclophosphamide. However, the response to the treatment is far from ideal; high rates of relapse in addition to low survival rates, 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 targets and develop novel specific therapies and early diagnostic methods. Consequently, there is a real need for drug carriers that fulfill these requirements for the different administration routes.
Recent advances in nanotechnology have shown high promise for the targeted delivery of personalized treatments using natural and engineered nanomaterials. Recently, hybrid organic-inorganic nanocomposites have been explored as synergistic approach that combines the modified bioactive release induced by the organic encapsulation, and the intrinsic physico-chemical properties of the inorganic counterpart. In particular, magnetic hybrids have the ability to combine both diagnosis and therapeutic functionalities in one single platform. However, the integration of these theranostic properties has been never applied to TNBC nor to solid tumours in general.
In terms of targeting, due to the particular lack of available receptors in TNBC, cellular populations have been interestingly described as targets or markers. In particular, Tumour Associated Macrophages (TAMs) are increasingly becoming main actors in advanced imaging and therapeutic efforts.
The main objective of this project is to ameliorate the prognosis of TNBC through the preparation and preclinical validation (in vitro plus in vivo) of a targeted theranostic probe able to specifically recognize and accumulate in TAMs, offering non-invasive imaging capabilities by MRI together with a synergic magnetic hyperthermia and chemotherapy treatment against TNBC. The expected results will enable translational research and will be key in the advance towards an adequate and timely therapeutic intervention in TNBC patients, being also a step forward on the way to targeted image-guided therapies of cancer.
In order to accomplish these goals, this exploratory project is conceived as a collaborative cross-disciplinary effort between INL, UT Austin and UMinho. Different expertise will be combined that will cover the preparation of the raw materials (UT Austin, INL), their assembly to prepare the targeted theranostic hybrids (INL) and the in vitro (UMinho, INL) and in vivo (INL, UT Austin) validation. According to the know-how of all three institutions, this project presents a reliable and feasible proposal.
This project has now finished. After an extension of 6 months due to Covid restrictions we have now managed to complete all the work proposed. We are analysing the data and preparing a manuscript to publish the results. We will share these results here as soon as they are published.