Xiao-Quan Yang

Folic acid-conjugated silica-coated gold nanorods and quantum dots for dual-modality CT and fluorescence imaging and photothermal therapy

Multifunctional nanoparticles (NPs) have great potential for multimodal cancer imaging and effective therapy. We have developed multifunctional NPs (GNR@SiO2@QDs) by incorporating gold nanorods (GNRs) and CdSe/ZnS quantum dots (QDs) into silica. Folic acid (FA) as a targeting ligand was covalently conjugated on the surfaces of GNR@SiO2@QDs with a silane coupling agent. Cell viability assay showed that these NPs had low cytotoxicity. And confocal fluorescence images illustrated that they could selectively target HeLa cells overexpressing folate receptors (FRs) rather than FR-deficient A549 cells. In vitro cell imaging experiments revealed that these NPs exhibited strong X-ray attenuation for X-ray computed tomography (CT) imaging and strong fluorescence for fluorescence imaging. They also showed an enhanced photothermal therapy (PTT) effect for cancer cells due to GNRs high absorption coefficient in the near infrared (NIR) region and a better heat generation rate. All results show that they have great potential in theranostic applications such as for targeted tumor imaging and therapy.

Multifunctional magnetic-hollow gold nanospheres for bimodal cancer cell imaging and photothermal therapy.

Multifunctional nanocomposites combining imaging and therapeutic functions have great potential for cancer diagnosis and therapy. In this work, we developed a novel theranostic agent based on hollow gold nanospheres (HGNs) and superparamagnetic iron oxide nanoparticles (SPIO). Taking advantage of the excellent magnetic properties of SPIO and strong near-infrared (NIR) absorption property of HGNs, such nanocomposites were applied to targeted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) of cancer cells. In vitro results demonstrated they displayed significant contrast enhancement for T2-weighted MRI and strong PAI signal enhancement. Simultaneously, the nanocomposites exhibited a high photothermal effect under the irradiation of the near-infrared laser and can be used as efficient photothermal therapy (PTT) agents for selective killing of cancer cells. All these results indicated that such nanocomposites combined with MRI-PAI and PTT functionality can have great potential for effective cancer diagnosis and therapy.

Facile Synthesis of Gold Nanospheres Modified by Positively Charged Mesoporous Silica, Loaded with Near-Infrared Fluorescent Dye, for in Vivo X-ray Computed Tomography and Fluorescence Dual Mode Imaging

We developed a simple and efficient method to synthesize a novel probe for both computed tomography (CT) and fluorescence imaging. Gold nanospheres were coated with positively charged mesoporous silica (Au@mSiO2-TTA) using a one-pot method to cohydrolyze quaternary ammonium silane and tetraethyl orthosilicate. Subsequently, IR-783, a negatively charged and water-soluble near-infrared fluorescent dye, was electrostatically adsorbed into the silica shell. Transmission electron microscopy imaging, X-ray powder diffraction, and energy dispersive X-ray spectroscopy indicated that Au@mSiO2-TTA had a clear core-shell structure, was monodisperse, had a large surface area (530 m2/g), and had a uniform pore size (2.2 nm). The mesoporous structure could effectively load fluorescent dye. After loading, the zeta potential of the nanoparticle dropped from 48 mV to 30 mV, and after additional modification with polyvinylpyrrolidone, it further reduced to 6 mV. Probe fluorescence was stable over time, and the probe was an effective CT contrast agent and as a near-infrared fluorescent probe. The half-life of the probe in the blood was 1.5 h, and the probe was mainly distributed in the spleen and liver 4 h after injection. Tissue sections showed that major organs were normal and without visible morphological changes, 6 days post injection, indicating the biocompatibility of the probe.

Reverse microemulsion-mediated synthesis of Bi2S3–QD@SiO2–PEG for dual modal CT–fluorescence imaging in vitro and in vivo

Monodispersed Bi2S3-QD@SiO2-PEG nanoparticles are prepared by a one-pot method in a reverse microemulsion system, which exhibited remarkable performances in CT and fluorescence imaging in vitro and in vivo.

In vitro and in vivo CT imaging using bismuth sulfide modified with a highly biocompatible Pluronic F127

Probe bismuth sulfide modified with Pluronic F127 (Bi2S3-PF127), which has high biocompatibility and dispersibility, is synthesized using triblock copolymer Pluronic F127 to modify hydrophobic Bi2S3 nanoparticles that are prepared by a hot injection method. TEM results show that most of the probe has a length of about 14.85xa0±xa01.70 nm and a breadth of about 4.79xa0±xa00.63 nm. After injected into the tail vein of a mouse, the probe has obvious CT contrast enhancement capability from x-ray CT imaging results. Meanwhile, the probes in vivo toxicity is also studied. It is found that hematoxylin and eosin stains of major organs have no change. A biochemical analysis (alanine aminotransferase and aspartate aminotransferase) prove the probe has no adverse effects. The results of a blood analysis (white blood cell count, red blood cell count, hemoglobin, and platelet count) are also normal. The biological distribution of Bi by ICP-AES shows that most of nanoparticles are cleaned out after injection 48 h, and the circulation half-life of the probe is 5.0 h, suggesting that Bi2S3-PF127 has a long circulation and indicating that the Bi2S3-PF127 probe has good biocompatibility and safety.

Hybrid nanoprobes of bismuth sulfide nanoparticles and CdSe/ZnS quantum dots for mouse computed tomography/fluorescence dual mode imaging

BackgroundX-ray computed tomography (CT) imaging can be used to reveal the three-dimensional structure of deep tissue with high spatial resolution. However, it cannot reveal molecular or cellular changes, and has great limitations in terms of specificity and sensitivity. Fluorescence imaging technology is one of the main methods used for the study of molecular events in vivo and has important applications in life science research. Therefore, the combination of CT and fluorescence imaging is an ideal dual-modal molecular imaging method, which can provide data on both molecular function and tissue structure, and has important research value. In a previous study, Bi2S3 nanoparticles were wrapped with quantum dots in SiO2 to generate CT and fluorescence imaging. However, this type of probe led to low survival and caused innegligible in vivo toxicity in mice. Therefore, it is necessary to develop new multifunctional probes that demonstrate biocompatibility and safety in vivo.MethodsA polyethylene glycol-phospholipid bilayer structure was used to synthesize hybrid clusters containing hydrophobic Bi2S3 nanoparticles and quantum dots for combined CT/fluorescence imaging. Mean particle size, polydispersity index, and zeta potential were used to study the stability over an 8-week test period. In vivo CT and fluorescence imaging experiments were performed, and the in vivo safety of the probe was evaluated, using histopathological, biochemical, and blood analyses.ResultsThe probe distinctly enhanced the CT contrast and had fluorescence imaging capability. In addition, the nanocomposite hybrid clusters showed a longer circulation time (>4xa0h) than iobitridol. The results also showed that the Bi2S3-QD@DSPE probe had good biocompatibility and safety, and did not affect normal organ functioning.ConclusionsBi2S3-QD@DSPE hybrid clusters exhibited remarkable performance in CT angiography and fluorescence imaging in vivo.

In Vivo Computed Tomography/Photoacoustic Imaging and NIR-Triggered Chemo–Photothermal Combined Therapy Based on a Gold Nanostar-, Mesoporous Silica-, and Thermosensitive Liposome-Composited Nanoprobe

Safe multifunctional nanoplatforms that have multiple therapeutic functions integrated with imaging capabilities are highly desired for biomedical applications. In this paper, targeted chemo-photothermal synergistic therapy and photoacoustic/computed tomography imaging of tumors were achieved by one novel multifunctional nanoprobe (GMS/DOX@SLB-FA); it was composed of a gold nanostar core and a doxorubicin (DOX)-loaded mesoporous silica shell (GMS), which was coated with a folic acid (FA)-modified thermosensitively supported lipid bilayer (SLB-FA) as a gatekeeper. The multifunctional probe had perfect dispersion and stability; 2.1 nm mesoporous pores and 208 nm hydration particle sizes were obtained. In vitro studies indicated that the drug-loaded probe had excellent ability to control the release of DOX, with 71.98 ± 2.52% cumulative release after laser irradiation, which was significantly higher than that of unirradiated control group. A survival rate of 72.75 ± 4.37% of HeLa cells at 57.75 μg/mL probe also demonstrated the low cytotoxicity of the targeted probe. Both in vitro and in vivo results showed that the probe could achieve targeted photoacoustic imaging of tumors because of the fact that the FA-modified probe could specifically recognize the overexpressed FA receptors on tumor cells; meanwhile, the probe could also achieve the chemo-photothermal synergistic therapy of tumors through controlling the drug release from mesoporous channels by a near-infrared laser. Therefore, the probe had great potential in the early diagnosis and treatment of cancer.

A multifunctional targeting probe with dual-mode imaging and photothermal therapy used in vivo

BackgroundAg2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation.Results200xa0nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50xa0μg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15xa0days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal.ConclusionsAg2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.

Folic acid modified Pluronic F127 coating Ag2S quantum dot for photoacoustic imaging of tumor cell-targeting

In this study, an oil-soluble Ag2S quantum dot (QD) was synthesized through thermal decomposition using the single-source precursor method, and Pluronic F127 (PF127), a triblock copolymer functionalized with folic acid (FA), was deposited on the surface of the QD, then a water-soluble PF127-FA@Ag2S nanoprobe with targeting ability was fabricated. The as-prepared PF127-FA@Ag2S exhibited spheroidal morphology and high dispersibility, with average diameters of 115xa0±xa020.7 nm (as observed by transmission electron microscopy). No obvious toxicity of the PF127-FA@Ag2S nanoprobe was found in standard 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and colony-formation assay, indicating good biocompatibility and safety. The resulting PF127-FA@Ag2S exhibited excellent stability between 4 °C-40 °C. Additionally, the capacity of the tumor cell-targeting high contrast enhanced photoacoustic imaging of PF127-FA@Ag2S was verified in comparison with A547 and HeLa cells. In other words, the excellent properties of PF127-FA@Ag2S show great potential in further research for targeting and photoacoustic imaging.

Graphene oxide coating core–shell silver sulfide@mesoporous silica for active targeted dual-mode imaging and chemo-photothermal synergistic therapy against tumors

The accurate treatment of tumors with the help of multimodality imaging is of great significance. Herein, a novel multifunctional probe combining active targeted fluorescent imaging (FL)/photoacoustic imaging (PA) and chemo-photothermal therapy for tumors has been designed. Targeting molecule folate (FA) modified graphene oxide (GO) was used to coat core-shell silver sulfide@mesoporous silica (QD@Si) while antitumoral doxorubicin (DOX) was loaded in mesoporous channels by electrostatic adhesion, and a delivery system (QD@Si-D/GO-FA) for active targeted dual-mode imaging and synergistic chemo-photothermal for tumors was successfully obtained. Experiments showed the cell survival rate was 76.3 ± 4.6% when the probe concentration reached 0.5 mg mL-1, and demonstrated that the probe had good biocompatibility. In vivo and in vitro results indicated that this probe could be used for active targeted FL/PA for tumors with overexpressed FA receptors. The temperature of the tumor rose to 63.5 °C under laser irradiation, and the tumor could be killed more effectively after combination with chemotherapy, which was caused by exfoliation of GO from QD@Si-D/GO-FA after irradiation. These results showed that the probe had great potential for application in oncology and is expected to provide evidence for early diagnosis and treatment of tumors.