Nanoparticle-mediated delivery of supramolecular drugs and biomolecules into cells

I. Introduction The successful transport of supramolecular drugs and biomolecule into living cells is highly important in biomedicine and pharmaceutics. Molecules alone usually cannot penetrate the cell membrane, therefore, an... [ view full abstract ]

I. Introduction
The successful transport of supramolecular drugs and biomolecule into living cells is highly important in biomedicine and pharmaceutics. Molecules alone usually cannot penetrate the cell membrane, therefore, an efficient carrier is needed. Calcium phosphate nanoparticles are well suited as a carrier for such molecules due to their high biodegradability and good biodegradability which is due to the fact that calcium phosphate is the inorganic mineral of human bone and teeth.1-3

II. Methods
Calcium phosphate nanoparticles were prepared by rapid precipitation and were loaded either with different artificial protein- and DNA-binders (polyfunctional anionic polymers, cationic calixarene dimers or amphiphilic molecular tweezers) or with fluorescently-labelled small and large biomolecules (nucleic acids, proteins or peptides). All nanoparticle dispersions were characterized by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and scanning electron microscopy (SEM). The amount of the fluorescing molecules on the nanoparticles was quantified by quantitative UV spectroscopy. The uptake of such fluorescence-labelled nanoparticles into HeLa cells was monitored by confocal laser scanning microscopy (CLSM). The cell viability was analyzed by an MTT assay.

III. Results
Functionalized calcium phosphate nanoparticles had a spherical morphology with a diameter between 150 and 200 nm (Figure 1). Neither the nanoparticle dispersions nor the dissolved molecules showed any cytotoxicity. As visualized by CLSM, the nanoparticles were easily taken up by HeLa cells together with their cargo molecules. In contrast, the dissolved molecules alone were not able to penetrate the cell membrane.

IV. Discussion
Calcium phosphate nanoparticles can serve as versatile carrier for small and large molecules across cell membranes. Such nanoparticles are efficiently taken up by cells where they can exert a biological or pharmaceutical function.
Figure 1: Scanning electron micrograph of calcium phosphate nanoparticles, functionalized with oligonucleotides.

References:
1. M. Epple et. al., J. Mater. Chem. 2010, 20, 18.
2. V. Sokolova et. al,. J. Nanoparticle Res. 2012, 14, 910.
3. O. Rotan et. al., Mater.-Wiss. u. Werkstofftechn. 2013, 44, 176.