Ping'an Ma

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.

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.

Rational Design of Multifunctional Upconversion Nanocrystals/Polymer Nanocomposites for Cisplatin (IV) Delivery and Biomedical Imaging

By combining upconversion nanoparticles with the cisplatin (IV) prodrug we have demonstrated that a stable and multifunctional drug delivery system can be designed that will both reduce the drawbacks of cisplatin and give insight in to its in vitro/in vivo imaging. The up/down-conversion fluorescence are detectable and show obvious co-localization, demonstrating that the nanoparticles are rather stable inside cells and retain the UCNPs and block copolymer.

Doxorubicin conjugated NaYF4:Yb3+/Tm3+ 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.

A facile fabrication of upconversion luminescent and mesoporous core–shell structured β-NaYF4:Yb3+, Er3+@mSiO2 nanocomposite spheres for anti-cancer drug delivery and cell imaging

Upconversion luminescent β-NaYF4:Yb3+, Er3+ nanoparticles (UCNPs) were encapsulated with uniform mesoporous silica shells, which were further modified with poly(ethylene glycol) (PEG) and cancer-targeting ligand folic acid (FA), resulting in the formation of water-dispersible and biologically functionalized core-shell structured UCNPs@mSiO2 nanoparticles with an overall average size of around 80 nm. The obtained multifunctional nanocomposite spheres can be performed as an anti-cancer drug delivery carrier and applied for cell imaging. It is found that anti-cancer drug doxorubicin hydrochloride (DOX) can be absorbed into UCNPs@mSiO2-PEG/FA nanospheres and released in a pH-sensitive pattern. In vitro cell cytotoxicity tests on cancer cells verified that DOX-loaded UCNPs@mSiO2-PEG/FA nanospheres exhibited greater cytotoxicity with respect to free DOX and DOX-loaded UCNPs@mSiO2-PEG at the same concentrations, owing to the increase of cell uptake of anti-cancer drug delivery vehicles mediated by the FA receptor. Moreover, the upconversion luminescence image of UCNPs@mSiO2-PEG/FA taken up by cells shows green emission under 980 nm infrared laser excitation, making the UCNPs@mSiO2-PEG/FA nanocomposite spheres promising candidates as bioimaging agents. These findings highlight the promise of the highly versatile multifunctional nanoparticles for simultaneous imaging and therapeutic applications.

Electrospinning-derived Tb2(WO4)3:Eu3+ nanowires: energy transfer and tunable luminescence properties

One-dimensional Tb(2)(WO(4))(3) and Tb(2)(WO(4))(3):Eu(3+) nanowires have been prepared by a combination method of sol-gel process and electrospinning. X-Ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), photoluminescence (PL), low voltage cathodoluminescence (CL) and time-resolved emission spectra as well as kinetic decays were used to characterize the resulting samples. The as-obtained precursor samples present fiber-like morphology with uniform size, and Tb(2)(WO(4))(3) and Tb(2)(WO(4))(3):Eu(3+) nanowires were formed after annealing. Under ultraviolet excitation and low-voltage electron beams excitation into WO(4)(2-) and the f-f transition of Tb(3+), the Tb(2)(WO(4))(3) samples show the characteristic emission of Tb(3+) corresponding to (5)D(4)-(7)F(6, 5, 4, 3) transitions due to an efficient energy transfer from WO(4)(2-) to Tb(3+), while Tb(2)(WO(4))(3):Eu(3+) samples mainly exhibit the characteristic emission of Eu(3+) corresponding to (5)D(0)-(7)F(0, 1, 2) transitions due to an energy transfer occurs from WO(4)(2-) and Tb(3+) to Eu(3+). The increase of Eu(3+) concentration leads to the increase of the energy transfer efficiency from Tb(3+) to Eu(3+). The PL color of Tb(2)(WO(4))(3):x mol% Eu(3+) phosphors can be tuned from green to red easily by changing the doping concentration (x) of Eu(3+), making the materials have potential applications in fluorescent lamps and color display fields.

Gelatin-encapsulated iron oxide nanoparticles for platinum (IV) prodrug delivery, enzyme-stimulated release and MRI

A facile method for transferring hydrophobic iron oxide nanoparticles (IONPs) from chloroform to aqueous solution via encapsulation of FITC-modified gelatin based on the hydrophobic-hydrophobic interaction is described in this report. Due to the existence of large amount of active groups such as amine groups in gelatin, the fluorescent labeling molecules of fluorescein isothiocyanate (FITC) and platinum (IV) prodrug functionalized with carboxylic groups can be conveniently conjugated on the IONPs. The nanoparticles carrying Pt(IV) prodrug exhibit good anticancer activities when the Pt(IV) complexes are reduced to Pt(II) in the intracellular environment, while the pure Pt(IV) prodrug only presents lower cytotoxicity on cancer cells. Meanwhile, fluorescence of FITC on the surface of nanoparticles was completely quenched due to the possible Förster Resonance Energy Transfer (FRET) mechanism and showed a fluorescence recovery after gelatin release and detachment from IONPs. Therefore FITC as a fluorescence probe can be used for identification, tracking and monitoring the drug release. In addition, adding pancreatic enzyme can effectively promote the gelatin release from IONPs owing to the degradation of gelatin. Noticeable darkening in magnetic resonance image (MRI) was observed at the tumor site after in situ injection of nanoparticles, indicating the IONPs-enhanced T2-weighted imaging. Our results suggest that the gelatin encapsulated Fe3O4 nanoparticles have potential applications in multi-functional drug delivery system for disease therapy, MR imaging and fluorescence sensor.

Fibrous-structured magnetic and mesoporous Fe3O4/silica microspheres: synthesis and intracellular doxorubicin delivery

A novel, fibrous-structured bifunctional (magnetic and mesoporous) Fe3O4/silica microsphere was successfully synthesized through a simple and economical self-assembled process in which hydrophobic 9 nm-Fe3O4nanocrystals were directly used without modifications. The obtained material is performed as a drug delivery carrier to investigate the in vitro and intracellular delivery properties of doxorubicin hydrochloride (DOX). X-Ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2adsorption/desorption, Fourier transform infrared spectroscopy (FT-IR), and superconducting quantum interference device (SQUID) were employed to characterize the composite. The results reveal that the novel composite exhibits typical mesoporous structure, narrow size distribution, good monodispersity, and superparamagnetic features. Notably, confocal laser scanning microscopy (CLSM) images indicate that the DOX-loaded sample could deliver DOX into the nuclei of HeLa cells to kill cells. Also, MTT assay confirms that the DOX-loaded sample leads to pronounced and efficient cytotoxic effects to L929 fibroblast cells, even similar to that of free DOX at high concentrations, whereas the pure material is non-toxic. Therefore, the novel material is expected to have potential application for targeted cancer therapy.

Poly(acrylic acid)-Modified Fe3O4 Microspheres for Magnetic-Targeted and pH-Triggered Anticancer Drug Delivery

Monodisperse poly(acrylic acid)-modified Fe(3)O(4) (PAA@Fe(3)O(4)) hybrid microspheres with dual responses (magnetic field and pH) were successfully fabricated. The PAA polymer was encapsulated into the inner cavity of Fe(3)O(4) hollow spheres by a vacuum-casting route and photo-initiated polymerization. TEM images show that the samples consist of monodisperse porous spheres with a diameter around 200 nm. The Fe(3)O(4) spheres, after modification with the PAA polymer, still possess enough space to hold guest molecules. We selected doxorubicin (DOX) as a model drug to investigate the drug loading and release behavior of as-prepared composites. The release of DOX molecules was strongly dependent on the pH value due to the unique property of PAA. The HeLa cell-uptake process of DOX-loaded PAA@Fe(3)O(4) was observed by confocal laser scanning microscopy (CLSM). After being incubated with HeLa cells under magnet magnetically guided conditions, the cytotoxtic effects of DOX-loaded PAA@Fe(3)O(4) increased. These results indicate that pH-responsive magnetic PAA@Fe(3)O(4) spheres have the potential to be used as anticancer drug carriers.

Well-dispersed KRE3F10 (RE = Sm–Lu, Y) nanocrystals: solvothermal synthesis and luminescence properties

A facile solvothermal route has been developed to synthesize a series of well-dispersed KRE3F10 (RE = Sm–Lu, Y) colloidal nanocrystals (NCs) with a rich variety of morphologies, such as hexagonal nanoplates, nanocubes and nanoparticles. X-Ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and photoluminescence (PL) spectra were used to characterize the samples. It is found that the formation of monodisperse nanocrystals closely correlates with the nature of the rare earth series from La to Lu, Y. Based on the experimental results, the possible growth mechanisms for products with diverse architectures have been presented. The obtained NCs are highly crystalline and can be well dispersed in cyclohexane to form stable and clear colloids, which all display self-activated luminescence due to the trap states of surface defects.