Transport of supramolecular drugs across the cell membrane by calcium phosphate nanoparticles

Many target sites of synthetic supramolecular drug molecules are located inside cells. Since larger and highly charged molecules are typically not able to cross the cell membrane on their own, an efficient carrier is needed. Calcium phosphate nanoparticles were loaded with different artificial protein and DNA binders, i.e. a polyfunctional anionic polymer, a cationic calixarene dimer and amphiphilic molecular tweezers. The loading of calcium phosphate nanoparticles with these molecules was quantitatively determined by UV spectroscopy. As visualized by fluorescence microscopy and confocal laser scanning microscopy (CLSM), the functionalized calcium phosphate nanoparticles were easily taken up by HeLa cells together with their cargo. In contrast, the dissolved molecules alone were not able to penetrate the cell membrane.