A versatile drug delivery system based on calcium phosphate/Eudragit®-E100 nanoparticles with a diameter below 200 nm was realized by a water-in-oil-in-water (W/O/W) emulsion solvent evaporation technique. Hydrophilic drugs (siRNA for gene silencing and bovine serum albumin as model protein) and hydrophobic drugs (5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphine, THPP, a photosensitizer for photodynamic therapy) were encapsulated as model drugs. Eudragit®-E100 is a poly(methyl methacrylate) copolymer with a low solubility at neutral pH and a high solubility at low pH. Thus, the particles are stable in cell culture media and rapidly dissolved in the lysosome after cellular uptake and delivery of their cargo into the cell. The particles had a positive charge (zeta potential +49 mV) and were taken up very well by epithelial cells (HeLa) as shown by fluorescence microscopy and confocal laser scanning microscopy. Gene-silencing experiments on HeLa-eGFP cells gave knockdown efficiencies of 39% with no toxic effects. The particles can be freeze-dried without cryoprotectant and easily redispersed in water, thus making their transport and storage convenient.