Hollow structured upconversion luminescent NaYF4:Yb3+, Er3+ nanospheres for cell imaging and targeted anti-cancer drug delivery

Uniform α-NaYF4:Yb3+, Er3+ nanospheres (∼130 nm) with mesoporous shell and hollow interior structure were synthesized by using Y(OH)CO3:Yb3+, Er3+ nanospheres (NPs) as sacrificial templates via a surface-protected “etching” and hydrothermal ion-exchange process. In this process, polyethylenimine (PEI) ligands played a key role in formation of the hollow structured α-NaYF4 nanospheres, i.e., they can effectively protect the surface of the Y(OH)CO3 from rapid dissolution by H+. Moreover, folic acid (FA), a commonly used cancer-targeting agent was conjugated on the surface of NPs based on the presence of free amine groups. The as-prepared FA-modified hollow NPs can be performed as anti-cancer drug carriers for the investigation of drug storage/release properties, which exhibit greater cytotoxicity than DOX-loaded α-NaYF4 NPs due to the specific cell uptake by HeLa cells via FA receptor-mediate endocytosis. Furthermore, upconversion (UC) luminescence images of FA-modified α-NaYF4:Yb3+, Er3+ NPs uptaken by cells shows bright green emission without background noise under 980 nm infrared laser excitation. Thus, these multifunctional nanospheres combining UC luminescent property and hollow and mesoporous structure have potential for simultaneous targeted anti-cancer drug delivery and cell imaging.