Barcoded spinel ferrite nanoparticles for in vivo targeting of tumor-infiltrating myeloid cells (TIMC)

• Applicant: Dr. Isabel Gessner
• Subject Area: Biomaterials
• Term: from 2020 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 444077706

Myeloid cells that are part of the innate immune system and play the key role in defending our body against infections have received increasing interest for cancer targeting since, only recently, emerging evidences indicate their active role within the microenvironment of tumors in promoting cancer growth and progression. Although it is known that these so-called tumor infiltrating myeloid cells (TIMC) heavily influence current cancer treatments, the function of each subtype and their classification into ‘good’ or ‘bad’ cells is still not completely understood. The aim of this project is thus the identification of new potential TIMC markers that could be used to distinguish pro- and anti-tumoral cells and specifically modulate their function. Spinel ferrite nanoparticles barcoded through incorporation of bivalent elements into the spinel matrix (MFe2O4 with M = Zn2+, Mn2+, Fe2+, Mg2+, etc.) will be used as carrier for potential TIMC targeting units. Myeloid cells will be extracted after injection of multiple nanoparticles into mice and evaluated with regard to their cellular heterogeneity via single cell RNA sequencing (scRNASeq) to differentiate between TIMC subtypes. The uptake and accumulation of spinel ferrites in specific subtypes will then be revealed using single cell inductively coupled plasma mass spectrometry (SC-ICP-MS). Identification of the nanoparticle core composition will reveal the selectivity and sensitivity of cell surface markers which will be a vital basis for the selective targeting of TIMC. This unique approach of combining single-cell analytics with the use of barcoded nanoparticles is expected to significantly enhance our understanding on myeloid cells and cancer development and represents an important stepstone for future immunotherapeutic approaches.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Ralph Weissleder