Two-wavelenght excited multilayer lanthanides-doped nanoparticles for cancer theranostics

Abstract

Recently properties of various nanoparticles and their application possibilities in medicine were investigated. Breakthrough in the field was made when rare earth doped upconverting nanoparticles were introduced. These nanoparticles can absorb and emit light in tissue optical transparency windows; also, they can emit ultraviolet (UV) light upon near-infrared (NIR) excitation (via process of upconversion), which can be used for activation of photo-drugs. Here, we show that rare earth metal ions doped nanoparticles can be used to create advanced tools for both cancer diagnostics and therapy – theranostic nanoparticles. These nanoparticles under 806 nm irradiation behave as high-contrast NIR-to-NIR optical markers and can be used to visualize the area of interest without any therapeutic effect. On the contrary, under 980 nm NIR irradiation, upconversion process is proceeded and UV/visible light is emitted, which can be used to excite photo-drug coupled to the nanoparticle and as a consequence initiate photochemical processes, causing damage to cancer cells. The aim of our study was to evaluate possibilities of multilayer decoupled LiYF4:Tm3+,Yb3+@LiYF4@LiYF4:Nd3+ nanoparticles (dNPs) and photosensitizer chlorine e6 (Ce6) complex in early cancer diagnostics and photosensitized tumor therapy. In this work dNPs emission spectra were measured upon 806 nm and 980 nm excitation to prove that we have NIR downshifting emission under heating-free 806 nm excitation and UV and blue radiation when dNPs are excited by the therapeutic 980 nm light. Spectral changes in Ce6 absorption spectrum were detected after dNDs-Ce6 complex was formed as the environment of Ce6 molecules has changed. LDH toxicity assay revealed that dNPs and dNPs-Ce6 complex had no dark toxicity for MDA-MB-231 and MCF-7 breast cancer cells. Also accumulation of dNPs and dNPs-Ce6 complex in MDA-MB-231 and MCF-7 cells was observed. It was shown that after incubation with dNPs-Ce6 complex and irradiation with 980 nm laser the cells have died, whereas irradiation with 806 nm laser had no toxic effect. Experiments with MDA-MB-231 spheroid cell cultures revealed that dNPs and dNPs-Ce6 complex have accumulated only in the periphery of spheroid and have not penetrated into the central part of the spheroid. Only the dNPs-Ce6 complex under 980 nm light induced damage to MDA-MB- 231 spheroid, while none effect was observed when the same complex was excited by the therapy-independent 806 nm light. Overall, these dNPs represent a new class of theranostic agents in which the therapy and diagnostics are not prompted simultaneously, but rather on-demand, hence potentially increasing the safety and versatility of such nanostructures in the future.