This thesis project focuses on pregnancy-associated breast cancer (PABC). It is estimated to affect 1 in every 3,000 pregnancies, with an increasing incidence in recent years. Currently, this disease poses a significant risk to maternal-fetal health due to its complex diagnosis and the substantial risks associated with existing cancer treatments, both for the mother and the fetus. These factors contribute to a worse prognosis compared to breast cancer in nonpregnant women.

In the absence of safe and effective treatments for cancer in pregnant women, the objective of this project is to develop nanotherapies that allow for effective treatment of PABC without compromising fetal health.

The project focuses on the use of polymeric nanoparticles as a platform for the safe delivery of drugs in pregnant women. The main approach is to design nanoparticles loaded with doxorubicin, the current standard drug for treating PABC, coated with "stealth" polymers such as poly(ethylene glycol) (PEG) or zwitterions, which reduce interaction with non-target cells and prevent transplacental passage. Additionally, these nanoparticles will be specifically targeted to breast cancer tumor cells through conjugation with active molecules, such as anisamide, which has an affinity for the sigma receptor present in most tumor cells and subtypes of breast cancer.

The project is structured into four objectives:

1. Synthesis of “stealth” polymers targeted to the sigma receptor, derived from poly(lactic-co-glycolic acid) (PLGA).
2. Formulation of nanoparticles loaded with doxorubicin that meet strict criteria for size (50–350 nm), surface charge (<5 mV), and stability (+6 months) to ensure their safety and efficacy.
3. In vitro validation: The selectivity and efficacy will be evaluated in cancer cell models and placental barrier models.
4. In vivo validation: Selectivity and efficacy will be tested in pregnant murine models of breast cancer.

Each of these steps is crucial to ensure that the nanoparticles selectively target tumor cells without affecting fetal development, enabling a safe and controlled treatment of PABC throughout pregnancy.

This project seeks to open a new line of research focused on improving maternal-fetal health, with special attention to oncology patients who currently represent an urgent and unmet need in the field of female reproductive health.