Biomimetic MAGnetic nanoparticles with homotypic targeting for combinatorial theraNOSTICS of triple-negative breast cancers

Ziel

Cancer is a leading cause of death and is a major impediment to increasing life expectancy around the globe. Amongst all breast cancers (BC), triple-negative breast cancers (TNBCs), are of much concern, as chemotherapy is the only option. However, it is associated with chemoresistance owing to drug efflux. Moreover, since TNBCs are negative for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER 2), treatment strategies targeting these receptors do not work. Combined strategies for TNBCs have strong potential in treating TNBCs, as compared to singular approaches. Thus, MAGNOSTICS aims to develop biomimetic cancer cell membrane (CCM) coated magnetic nanoparticles for chemotherapy, gene targeting, and magnetic hyperthermia as a triple strategy for TNBC therapy. In addition, MAGNOSTICS proposes multimodal theranostics incorporating MRI enabled by MNPs. To promote cellular uptake and immune escape, MNPs will be loaded with CDDP and siRNA and camouflaged with CCM derived from TNBC cells. CCM coating will utilize the homotypic targeting strategy for self-recognition and uptake of NPs. Thus, the objectives are; i) to synthesize and characterize CCM coated MNPs conjugated with CDDP and siABCB1, ii) to study the biocompatibility/uptake and single therapeutic strategies as proof-of-concept in 2D cell cultures, iii) To develop 3D multicellular tumor spheroids and demonstrate the effectiveness of camouflaged NPs as combined theranostic platform; iv) to ensure further professional development of the ER through training, dissemination and public engagement. MAGNOSTICS thus aims to improve TNBC treatment and impact society with the right term and place.