One-step synthesis of small-sized and water-soluble NaREF4 upconversion nanoparticles for in vitro cell imaging and drug delivery.

Small (2-28 nm) NaREF(4) (rare earth (RE)=Nd-Lu, Y) nanoparticles (NPs) were prepared by an oil/water two-phase approach. Meanwhile, hydrophilic NPs can be obtained through a successful phase-transition process by introducing the amphiphilic surfactant sodium dodecylsulfate (SDS) into the same reaction system. Hollow-structured NaREF(4) (RE=Y, Yb, Lu) NPs can be fabricated in situ by electron-beam lithography on solid NPs. The MTT assay indicates that these hydrophilic NPs with hollow structures exhibit good biocompatibility. The as-prepared hollow-structured NPs can be used as anti-cancer drug carriers for drug storage/release investigations. Doxorubicin hydrochloride (DOX) was taken as model drug. The release of DOX from hollow α-NaLuF(4):20% Yb(3+), 2% Er(3+) exhibits a pH-sensitive release patterns. Confocal microscopy observations indicate that the NPs can be taken up by HeLa cells and show obvious anti-cancer efficacy. Furthermore, α-NaLuF(4):20% Yb(3+), 2% Er(3+) NPs show bright-red emission under IR excitation, making both the excitation and emission light fall within the "optical window" of biological tissues. The application of α-NaLuF(4):20% Yb(3+), 2% Er(3+) in the luminescence imaging of cells was also investigated, which shows a bright-red emission without background noise.

Yang D ，Dai Y ，Ma P ，Kang X ，Cheng Z ，Li C ，Lin J ... -  《-》

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.

Yang D ，Kang X ，Ma P ，Dai Y ，Hou Z ，Cheng Z ，Li C ，Lin J ... -  《-》

Doxorubicin conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles for therapy and sensing of drug delivery by luminescence resonance energy transfer.

In this study, we report an anticancer drug delivery system based on doxorubicin (DOX)-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles. The as-synthesized nanoparticles consist of uniform spherical nanoparticles with an average diameter of 25 nm. The drug delivery system demonstrates the ability to release DOX by cleavage of the hydrazone bond in mildly acidic environments. The spectra overlap between emission of donor NaYF(4):Yb(3+)/Tm(3+) nanoparticles at 452 nm ((1)D(2)→(3)F(4)) and 477 nm ((1)G(4)→(3)H(6)) and the broad absorbance of acceptor DOX centered at around 480 nm enables energy transfer to occur between the nanoparticles and DOX. The quenching and recovery of the up-conversion luminescence of NaYF(4):Yb(3+)/Tm(3+) by DOX due to luminescence resonance energy transfer (LRET) mechanism are applied as optical probe to confirm the DOX conjunction and monitor the release of DOX. The DOX-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles exhibit an obvious cytotoxic effect on SKOV3 ovarian cancer cells via MTT assay. Meanwhile, the endocytosis process of DOX-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles by SKVO3 cells was demonstrated through confocal laser scanning microscopy (CLSM), flow cytometry and ICP-OES. Such drug delivery system, which combines pH-triggered drug-release and up-converting nanoparticles-based LRET property, has excellent potential applications in cancer therapy and smart imaging.

Dai Y ，Yang D ，Ma P ，Kang X ，Zhang X ，Li C ，Hou Z ，Cheng Z ，Lin J ... -  《-》

Rare-Earth nanoparticles with enhanced upconversion emission and suppressed rare-Earth-ion leakage.

Upconversion emissions from rare-earth nanoparticles have attracted much interest as potential biolabels, for which small particle size and high emission intensity are both desired. Herein we report a facile way to achieve NaYF(4):Yb,Er@CaF(2) nanoparticles (NPs) with a small size (10-13 nm) and highly enhanced (ca. 300 times) upconversion emission compared with the pristine NPs. The CaF(2) shell protects the rare-earth ions from leaking, when the nanoparticles are exposed to buffer solution, and ensures biological safety for the potential bioprobe applications. With the upconversion emission from NaYF(4):Yb,Er@CaF(2) NPs, HeLa cells were imaged with low background interference.

Wang YF ，Sun LD ，Xiao JW ，Feng W ，Zhou JC ，Shen J ，Yan CH ... -  《-》

Multifunctional rare-earth self-assembled nanosystem for tri-modal upconversion luminescence /fluorescence /positron emission tomography imaging.

Rare-earth upconversion nanoparticles (UCNP) which can absorb low-energy photons and emit high energy photons have attracted great interest not only because of their unique application in upconversion luminescence imaging, but also because they can be used as ideal building blocks for multimodal bioimaging probes. Improving the water-solubility of UCNP and functionalizing them are as yet unresolved problems. In this present study, a general strategy was developed to achieve these two aims by converting hydrophobic upconversion nanoparticles into hydrophilic ones. This was based on the self-assembly between oleic acid, which is a capping ligand, as the guest molecule, and alpha-cyclodextrin, as the host molecule, no matter what the particle size was (10-400 nm) or what synthesis method (thermal decomposition, hydrothermal, solvothermal) was used. The synthesized hydrophilic nanoparticles can further load hydrophobic molecule, e.g. Os(II) complex. The process of self-assembly and loading was confirmed by transmission electron microscopy, X-ray powder diffraction, (1)H-nuclear magnetic resonance, Fourier transform-infrared and thermogravimetric analysis, upconversion luminescence and fluorescence spectra. Further bioapplication has also been investigated, including cell-labeling, in vivo lymphatic imaging, upconversion luminescence and positron emission tomography imaging of whole-body Kunming mice. The results indicate that this method is a potential candidate for the preparation of hydrophilic UCNP as a multimodal nanoprobe.

Liu Q ，Chen M ，Sun Y ，Chen G ，Yang T ，Gao Y ，Zhang X ，Li F ... -  《-》