Due to their distinct optical properties, lanthanide based upconverting nanoparticles (UCNPs) have aroused considerable interest in the field of biomedicine during the last years. The basic principle relies on the absorption of low energy near infrared (NIR) light and the subsequent emission of higher energy light covering the visible to NIR regions, which enables a ‘cell-friendly’ excitation with high penetration depth but low autofluorescence. In order to employ UCNPs for cancer theranostics, loading with a drug, which is released at the place of interest, is in great demand. Nevertheless, it still remains a great challenge to observe the successful drug release in the cells. We developed a UCNP-based drug delivery vehicle embedding the fluorophore Cy3 as a model for a drug into a layered albumin shell around the UCNP and studied the suitability of the resulting construct for optical monitoring of drug release.
In this approach, oleate-capped UCNPs codoped with Er3+ (2%) and Yb3+ (20%) were prepared by the well-established thermal decomposition method, whereby oleic acid functioned as a solvent and as a surface active molecule. After removal of the hydrophobic ligand, the UCNPs were coated with several layers of human serum albumin (HSA) and polyallylamine hydrochloride (PAH) using a layer by layer approach. Successful attachment of each layer was proven by measuring strongly alternating zeta-potentials of the UCNPs.
Seeking better understanding of drug release from UCNP-based vehicles, fluorophore Cy3 was chosen as model, as its absorbance has a significant overlap with the green emission band of Er3+ doped into the UCNPs, thus an energy transfer between both units is expected. Since this transfer is known to be highly distance dependent, the fluorophore was incorporated into various HSA layers with increasing space to the UCNP surface.
In fact, optical measurements after excitation with a 980 nm laser revealed a reduced UCNP emission in the presence of the dye and an additional emission peak of the latter. This effect was both, concentration and distance dependent, which proves the suitability of the as-prepared nanoplatform as a model to monitor drug release from a nanoparticle-based delivery vehicle.