Xuechuan Gao

Controllable Synthesis of a Smart Multifunctional Nanoscale Metal–Organic Framework for Magnetic Resonance/Optical Imaging and Targeted Drug Delivery

As a result of their extraordinarily large surfaces and well-defined pores, the design of a multifunctional metal-organic framework (MOF) is crucial for drug delivery but has rarely been reported. In this paper, a novel drug delivery system (DDS) based on nanoscale MOF was developed for use in cancer diagnosis and therapy. This MOF-based tumor targeting DDS was fabricated by a simple postsynthetic surface modification process. First, magnetic mesoporous nanomaterial Fe-MIL-53-NH2 was used for encapsulating the drug and served as a magnetic resonance contrast agent. Moreover, the Fe-MIL-53-NH2 nanomaterial exhibited a high loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, the fluorescence imaging agent 5-carboxyfluorescein (5-FAM) and the targeting reagent folic acid (FA) were conjugated to the 5-FU-loaded Fe-MIL-53-NH2, resulting in the advanced DDS Fe-MIL-53-NH2-FA-5-FAM/5-FU. Owing to the multifunctional surface modification, the obtained DDS Fe-MIL-53-NH2-FA-5-FAM/5-FU shows good biocompatibility, tumor enhanced cellular uptake, strong cancer cell growth inhibitory effect, excellent fluorescence imaging, and outstanding magnetic resonance imaging capability. Taken together, this study integrates diagnostic and treatment aspects into a single platform by a simple and efficient strategy, aiming for facilitating new possibilities for MOF use for multifunctional drug delivery.

Inorganic Nanovehicle for Potential Targeted Drug Delivery to Tumor Cells, Tumor Optical Imaging

In this work, an inorganic multifunctional nanovehicle was tailored as a carrier to deliver anticancer drug for tumor optical imaging and therapy. The nanovehicle could be used as a dually targeted drug nanovehicle by bonded magnetical (passive) and folic acid (active) targeting capabilities. In addition, it was developed using rhodamine 6G (R6G) as a fluorescence reagent, and an α-zirconium phosphate nanoplatform (Zr(HPO4)2·H2O, abbreviated as α-ZrP) as the anticancer drug nanovehicle. The novel drug-release system was designed and fabricated by intercalation of α-ZrP with magnetic Fe3O4 nanoparticles and anticancer drug 5-fluorouracil (5-FU), followed by reacting with a folate acid-chitosan-rhodamine6G (FA-CHI-R6G) complex, and then α-ZrP intercalated with Fe3O4 nanoparticles and 5-fluorouracil (5-FU) was successfully encapsulated into chitosan (CHI). The resultant multifunctional drug delivery system was characterized by scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray analysis, photoluminescence spectra, magnetometry, fluorescence microscopy imaging studies and other characterization methods. Simultaneously, the drug release in vitro on the obtained nanocomposites that exhibited a sustained release behavior was carried out in buffer solution at 37 °C, which demonstrated clearly that the nanocomposites shown a sustained release behavior. Meanwhile, cell culture experiments also indicated that the drug-release system had the potential to be used as an dually targeted drug nanovehicle into the tumor cells.

Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.

A synthesis and up-conversional photoluminescence study of hexagonal phase NaYF4:Yb,Er nanoparticles

In this article, hexagonal phase NaYF4:Yb,Er (β-NaYF4:Yb,Er) nanoparticles with a controlled size and morphology were synthesized via a simple and environmentally friendly method under relatively mild conditions. The different F−/Y3+ molar ratios were used in the synthesis of hexagonal Yb3+,Er3+ codoped NaYF4 nanocrystals as a means of controlling the size and morphology of the nanocrystals. Subsequently, the morphology and structure of the products were characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). The effect of the F−/Y3+ molar ratio on the size and morphology of the products was examined. When the F−/Y3+ molar ratio was gradually increased, the products transformed from spherical hexagonal nanocrystals to regular hexagonal nanocrystals and the size of the products changed from 8 to 400 nm. That is to say, excessive F− ions were capable of accelerating for the formation of larger β-NaYF4:Yb,Er nanoparticles in our synthesis procedure. Meanwhile the upconversion photoluminescence of the nanocrystals was investigated in detail by fluorescent spectroscopy to reveal the relationship between the optical properties and the morphology and size of the products. As a consequence, the upconversion photoluminescence of the nanocrystals demonstrated a morphology and size dependence. Thus the fabrication of β-NaYF4:Yb,Er nanoparticles with different sizes and morphologies would satisfy the diverse requirements in various fields.

Synthesis of monodisperse Bi2O3-modified CeO2 nanospheres with excellent photocatalytic activity under visible light

In this work, monodisperse CeO2/Bi2O3 nanospheres were successfully synthesized via the three-step method, which is a traditional hydrothermal dip-coating–anneal method, and subsequent facile calcination at 600 °C for 4 h. The structure of obtained products was characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM). The results showed that highly uniform CeO2 microspheres and monodisperse CeO2/Bi2O3 nanospheres were obtained, the sizes of CeO2 microspheres and CeO2/Bi2O3 nanospheres were ~100 nm and ~125 nm. Besides that, the photocatalytic activities of CeO2/Bi2O3 nanocomposites were evaluated by photodegradation of Rhodamine B (RhB) under visible light. CeO2/Bi2O3 nanospheres exhibited a wide visible-light absorption with an edge at ca. 800 nm, which indicated a wide red shift compared to that of individual CeO2 microspheres (ca. 450 nm) and individual Bi2O3 nanoparticles (ca. 450 nm). Furthermore, the obtained CeO2/Bi2O3 nanospheres had remarkable photocatalytic degradation activities of dye under visible light compared with the activities of two individual photocatalysts of CeO2 microspheres and Bi2O3 NPs with the same concentration. The higher photocatalytic degradation activities of the photocatalysts could be ascribed to the following factors: (1) a large specific surface area of CeO2/Bi2O3 nanospheres with small size, (2) the efficient separation of photogenerated electrons and holes of the photocatalysts, and (3) a wide visible-light photoabsorption range (700 nm > λ > 400 nm). Therefore, small monodisperse CeO2/Bi2O3 nanospheres were designed by a simple route with efficient photocatalytic activity.

Fabrication and characterization of novel magnetic/luminescent multifunctional nanocomposites for controlled drug release

In this study, a new kind of multifunctional drug-release system combined with the interesting properties of up-conversion fluorescence, magnetism and controlled drug release was successfully prepared by encapsulation of NaYF4:Yb,Er nanocrystals, Fe3O4 functionalized α-ZrP nanocomposites and gentamicin sulfate (GS) with chitosan (CHI). In this system, the NaYF4:Yb,Er nanocrystals were adsorbed on the surface of zirconium bis-(monohydrogen orthophosphate) monohydrate (α-ZrP), while GS and Fe3O4 nanoparticles were intercalated into the interlayer of α-ZrP. Additionally, a thin layer of chitosan enwrapped the above nanocomposites. The resultant nanocomposites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX) analysis, photoluminescence spectra (PL), magnetometry and other characterization methods. The results revealed that the as-prepared multifunctional nanocomposites exhibited efficient upconversion luminescence and magnetism that had potential in magnetic separation and bioimaging. Meanwhile, in vitro drug release tests using the obtained nanocomposites (pH 7.4 buffer solution at 37 °C) indicated that the nanocomposites exhibited a prolonged drug release rate. Further, the antibacterial activity of GS released from the system on Gram-negative Escherichia coli was tested. Our results suggested that the obtained multifunctionalized nanomaterials could take full advantage of each component, and might be very attractive for a variety of biomedical applications, such as bioimaging, drug targeting and bioseparation.

One-pot synthesis of hierarchical-pore metal–organic frameworks for drug delivery and fluorescent imaging

Metal–organic frameworks (MOFs) have attracted significant interest for drug delivery. However, MOFs usually have micropores smaller than 2 nm, restraining larger drug molecules from entering into the pores of MOFs, restricting their practical application as drug carriers. Here we demonstrate a novel one-step approach to synthesize a fluorescent hierarchical-pore metal–organic framework (H-MOF), which is realized by assembling a MOF in an aqueous solution containing rhodamine b (RhB) as a modulator and a fluorescent imaging reagent. The as-synthesized fluorescent H-MOF can not only serve as a substrate to in situ load micromolecule and macromolecular drugs simultaneously, but can also efficiently deliver the drugs into cells. The red fluorescence of RhB remains in the H-MOF, avoiding the interference of auto-fluorescence in vivo imaging and realizing high quantum yield and low-background imaging. The low cytotoxicity, good biocompatibility and high imaging efficiency of the fluorescence H-MOF are confirmed using murine gastric cancer 803 (MGC-803) cells and human airway smooth muscle cell (HASMC) as modes. Good stability and distribution in vivo are confirmed using naked mouse as modes. Taken together, we demonstrate the possibility of using one-step method to obtain fluorescent H-MOF, aiming for loading various drug molecules and bioimaging, which probably is useful for some specific requirements of pharmaceuticals.

Fabrication and potential application of a di-functional magnetic system: magnetic hyperthermia therapy and drug delivery

A novel di-functional system was synthesized by encapsulation of superparamagnetic Fe3O4 and a therapeutic agent 5-fluorouracil (5-Fu) with the thermo-responsive poly(N-isopropylacrylamide) (PNIPAM), which was coated with mesoporous SiO2 nanoparticles in a mesoporous core–shell structure. The system featured functionalized magnetic Fe3O4 and a smart thermo-responsive polymer PNIPAM. In an alternating magnetic field (AMF), the magnetic nanoparticles were heated up to 45 °C, which was the cancer treatment temperature. Therefore, it has potential for hyperthermia treatment. The smart polymer PNIPAM has a lower critical solution temperature (LCST), which is representative of a phase transition behavior. Based on it, the thermo-responsive polymer PNIPAM played a role of an on-off trigger switch in the process of drug releasing. The tests of drug releasing were investigated by UV-visible spectrophotometry at 45 °C and 25 °C. The test results showed that there was little drug released at 25 °C (below the LCST) but drug was mainly released at the temperature of 45 °C (above the LCST). In a word, our studies were mainly about the di-function of the composite: magnetic hyperthermia treatment and drug release. It has potential applications for reducing side effects of cancer treatment and achieving controlled drug release in response to variations of temperature.

Size and surface controllable metal–organic frameworks (MOFs) for fluorescence imaging and cancer therapy

Benefiting from their porous structures, metal-organic frameworks (MOFs) have attracted intensive attention for use in drug release. However, the controllable synthesis of MOFs with proper particle sizes is still very challenging, which largely limits its applications. Here, UIO-66-NH2 with controlled particle sizes in the range of 20-200 nm has been achieved successfully. The amine on UIO-66-NH2 is demonstrated for the feasible post-modifying of UIO-66-NH2 to obtain multifunctional MOFs, overcoming the limitations of functional simplicity and broadening the range of applications. After covalent grafting the targeting reagent folic acid (FA) and the fluorescence imaging agent 5-carboxyfluorescein (5-FAM), UIO-66-NH2-FA-5-FAM/5-FU can target the cancer cells HePG-2 and display excellent fluorescence imaging in vitro. Moreover, the in vivo biodistribution and antitumor assays indicate that UIO-66-NH2-FA-5-FAM/5-FU can accumulate in the tumor and display stronger antitumor efficiency due to the long-time drug release. Taken together, this study integrates the imaging section and the treated section in a single platform successfully and the present approach can be a good use of therapeutic MOFs to achieve the desired objective, a better treatment.

Bifunctional dual-modal luminescence nanocomposites: grafting down luminescence onto core–shell, up-conversional silica nanoarchitecture

Dual-modal luminescence nanocomposites (NCs) were successfully prepared via a facile and versatile strategy by coating the down-shifting emission (DS) ZnO quantum dots (QDs) onto core–shell NCs, in which up-conversion (UC) luminescence NaYF4:Yb3+, Er3+/Tm3+ nanoparticles (NPs) were coated by SiO2. The as-prepared NCs were characterized by X-ray powder diffraction (XRD), high resolution transmission electron microscopy (HRTEM), energy dispersive X-ray (EDX) analysis, nitrogen adsorption–desorption isotherms and other characterization methods. Due to both their strong NIR-to-visible upconversion luminescence under 980 nm excitation and bright visible emission under UV irradiation, the dual-mode luminescent NCs are potentially useful in highly sensitive fluorescent labeling, which may attract wide attention from the fields of chemistry, materials, nanotechnology, nanobiotechnology and nanomedicine.