1. Synergistic Combination of Calcium and Citrate in Mesoporous Nanoparticles Targets Pleural Tumors
- Author
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Constantin von Schirnding, Georgios T. Stathopoulos, Karin Bartel, Ann-Katrin Sommer, Marina Lianou, Lisa Wehl, Hanna Engelke, Ernst Wagner, Angelika M. Vollmar, Stefan Datz, Veronika Weiß, Franz Geisslinger, Christoph Bräuchle, Giannoula Ntaliarda, Thomas Bein, Adam Hermawan, Andreas Roidl, Johann M. Feckl, Ioanna Giopanou, and Bernhard Illes
- Subjects
General Chemical Engineering ,Cell ,chemistry.chemical_element ,Nanoparticle ,02 engineering and technology ,Calcium ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Materials Chemistry ,medicine ,Environmental Chemistry ,Adverse effect ,Biochemistry (medical) ,General Chemistry ,021001 nanoscience & nanotechnology ,Phosphate ,0104 chemical sciences ,medicine.anatomical_structure ,chemistry ,Toxicity ,Cancer cell ,Systemic administration ,0210 nano-technology - Abstract
Summary Conventional chemotherapy leads to severe adverse effects since it involves systemic administration of toxic drugs at high dosage. Unlike traditional chemotherapeutics, calcium phosphate and citrate have both been discussed as very promising anticancer agents and are not inherently toxic. Yet, their breakthrough has been hampered by the lack of an administration approach that overcomes the strict regulatory mechanisms of the cell. Here, we present a combinatorial administration of calcium, phosphate, and citrate as colloidal, amorphous nanoparticles (CPCs) that selectively kill cancer cells without involvement of inherently toxic drugs. The particles are toxic neither before endosomal release nor after their degradation. This highly selective toxicity allowed us to successfully treat two different aggressive pleural tumors in mice, reducing their size by about 40% and 70% after only two local applications. Safety assessment studies over 2 months show no signs of adverse effects except for slightly enhanced pleural thickening after eight applications.
- Published
- 2021