Multilayer Dual-Polymer-Coated Upconversion Nanoparticles for Multimodal Imaging and Serum-Enhanced Gene Delivery

Upconversion nanoparticles (UCNPs) have been widely explored for various bioapplications because of their unique optical properties, easy surface functionalization, and low cytotoxicity. Herein, we synthesize gadolinium (Gd3+)-doped UCNPs, which are modified first with poly(ethylene glycol) (PEG) and then with two layers of poly(ethylenimine) (PEI) via covalent conjugation and layer-by-layer assembly, respectively. Compared with UCNP-PEG@1×PEI with only one layer of PEI coating, the final complex, UCNP-PEG@2×PEI, with two PEI layers exhibits reduced cytotoxicity and enhanced gene transfection efficiency. It is interesting to find that while free PEI polymer is only effective in gene transfection in a serum-free medium and shows drastically reduced transfection ability if serum is added, UCNP-PEG@2×PEI is able to transfect cells in both serum-free and -containing media and, surprisingly, offers even higher gene transfection efficiency if serum is added. This is likely due to the formation of protein corona on the nanoparticle surface, which triggers the receptor-mediated endocytosis of our UCNP vectors. Considering the upconversion luminescence and magnetic resonance imaging contrasting ability of UCNPs, our novel nanovector could serve as a "trackable" gene-delivery carrier promising for theranostic applications.