Abstract 5068: Functionalized superparamagnetic nanoparticles for theranostics of membrane-bound Hsp70 positive malignant brain tumors

Abstract

Biomedical nanotechnologies based on superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising instrument for malignant brain tumor theranostics. Due to their unique physico-chemical properties, they can be used for multimodal cancer therapy (including hyperthermia), diagnostics, and targeted delivery of therapeutic molecules. To enhance the tumor-homing properties of nanoparticles the latter were conjugated with bioligands (i.e., monoclonal antibodies, Fab-fragments, peptides, and proteins such serine protease granzyme B) that recognize 72 kDa membrane-bound heat shock protein (mHsp70) that is expressed on the plasma membrane of tumor cells, including multiforme glioblastoma (GBM), but not on normal corresponding cells. Therapeutic potential of magnetic conjugates can be attenuated by binding to the particles surface of granzyme B (GrB-SPIONs) that exerts pro-apoptotic activity. Functionalized particles significantly contrast-enhanced the orthotopic glioblastoma (U87 glioma in NMRI nu/nu mice, GL261 glioma in C57/Bl6 mice) in preclinical animal models when high-field (11 ) magnetic resonance tomography (Bruker) was employed. Furthermore, when GrB-SPIONs were applied, we detected a statistically significant delay of tumor progression and increase of overall animal survival. Anti-tumor activity of GrB-SPIONs was further synergistically potentiated by stereotactic radiotherapy combined with immune check-point inhibitors (i.e., CTLA-4). In conclusion, synthesized superparamagnetic nanoparticles targeting mHsp70-positive could be employed for theranostics of malignant brain tumors and translated into further clinical trials.This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement № 075-15-2020-901). Citation Format: Ruslana Tagaeva, Vyacheslav Fedorov, Natalia Yudintceva, Luidmila Yakovleva, Boris Nikolaev, Veronica Osnach, Maxim Shevtsov. Functionalized superparamagnetic nanoparticles for theranostics of membrane-bound Hsp70 positive malignant brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5068.