Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and multimodal imaging probes.

A new type of drug-delivery system (DDS) was constructed, in which the anti-cancer drug doxorubicin (DOX) was conjugated to the ultra-small sized (sub-10 nm) BaGdF5:Yb(3+)/Tm(3+) based upconversion nanoparticles (UCNPs). This multifunctional DDS simultaneously possesses drug delivery and optical/magnetic/X-ray computed tomography imaging capabilities. The DOX can be selectively released by cleavage of hydrazone bonds in acidic environment, which shows a pH-triggered drug release behavior. The MTT assay shows these DOX-conjugated UCNPs exhibit obvious cytotoxic effect on HeLa cells. Moreover, to improve the upconversion luminescence intensity, core-shell structured UCNPs were constructed. The in vitro upconversion luminescence images of these UCNPs uptaken by HeLa cells show bright emission with high contrast. In addition, these UCNPs were further explored for T1-weighted magnetic resonance (MR) and X-ray computed tomography (CT) imaging in vitro. Long-term in vivo toxicity studies indicated that mice intravenously injected with 10 mg/kg of UCNPs survived for 40 days without any apparent adverse effects to their health. The results indicate that this multifunctional drug-delivery system with optimized size, excellent optical/MR/CT trimodal imaging capabilities, and pH-triggered drug release property is expected to be a promising platform for simultaneous cancer therapy and bioimaging.

Yang D ，Dai Y ，Liu J ，Zhou Y ，Chen Y ，Li C ，Ma P ，Lin J ... -  《-》

Multifunctional upconversion mesoporous silica nanostructures for dual modal imaging and in vivo drug delivery.

Incorporating the agents for magnetic resonance imaging (MRI), optical imaging, and therapy in one nanostructured matrix to construct multifunctional nanomedical platform has attracted great attention for simultaneous diagnostic and therapeutic applications. In this work, a facile methodology is developed to construct a multifunctional anticancer drug nanocarrier by combining the special advantages of upconversion nanoparticles and mesoporous silica. β-NaYF4 :Yb(3+) , Er(3+) @β-NaGdF4 :Yb(3+) is chosen as it can provide the dual modality of upconversion luminescence and MRI. Then mesoporous silica is directly coated onto the upconversion nanoparticles to form discrete, monodisperse, highly uniform, and core-shell structured nanospheres (labeled as UCNPs@mSiO2 ), which are subsequently functionalized with hydrophilic polymer poly(ethylene glycol) (PEG) to improve the colloidal stability and biocompatibility. The obtained multifunctional nanocomposites can be used as an anticancer drug delivery carrier and applied for imaging. The anticancer drug doxorubicin (DOX) is absorbed into UCNPs@mSiO2 -PEG nanospheres and released in a pH-sensitive pattern. In vitro cell cytotoxicity tests on cancer cells verify that the DOX-loaded UCNPs@mSiO2 -PEG has comparable cytotoxicity with free DOX at the same concentration of DOX. In addition, the T1 -weighted MRI that measures in aqueous solutions reveals that the contrast brightening increases with the concentration of Gd(3+) component. Upconversion luminescence images of UCNPs@mSiO2 -PEG uptaken by cells show green emission under 980 nm infrared laser excitation. Finally, the nanocomposites show low systematic toxicity and high in vivo antitumor therapy efficacy. These findings highlight the fascinating features of upconversion-mesoporous nanocomposites as multimodality imaging contrast agents and nanocarrier for drug molecules.

Li C ，Yang D ，Ma P ，Chen Y ，Wu Y ，Hou Z ，Dai Y ，Zhao J ，Sui C ，Lin J ... -  《-》

Optimization of upconversion luminescence of Nd(3+)-sensitized BaGdF5-based nanostructures and their application in dual-modality imaging and drug delivery.

He F ，Li C ，Zhang X ，Chen Y ，Deng X ，Liu B ，Hou Z ，Huang S ，Jin D ，Lin J ... -  《-》

Design of multifunctional alkali ion doped CaF2 upconversion nanoparticles for simultaneous bioimaging and therapy.

Yin W ，Tian G ，Ren W ，Yan L ，Jin S ，Gu Z ，Zhou L ，Li J ，Zhao Y ... -  《-》

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 ... -  《-》