Huiqing Zhong

Graphene oxide based surface-enhanced Raman scattering probes for cancer cell imaging

The intrinsic Raman signals provide the potential of graphene oxide (GO) for cellular imaging. Herein, novel surface-enhanced Raman scattering (SERS) labels based on GO-Ag nanoparticle (NP) composites are developed for fast cellular probing and imaging. The optimum SERS signals of the hybrids can be well controlled by adjusting the weight ratio between AgNO(3) and GO. Utilizing GO-AgNPs as the highly sensitive optical probes, fast SERS imaging of cancer cells is realized with a very short integration time of about 0.06 s per pixel. Furthermore, folic acid (FA) is covalently conjugated to GO for targeting specific cancer cells with folate receptors (FRs). Targeted SERS images can be acquired after 2 h incubation with FA-GO-AgNPs, which are specifically located on the surface of FR-positive cancer cells. In conclusion, the GO-based Raman probes mentioned here open up exciting opportunities for biomedical imaging.

In vivo quantification of propylene glycol, glucose and glycerol diffusion in human skin with optical coherence tomography

The purpose of study is to quantify and compare diffusion of propylene glycol, glucose, glycerol in the human skin in vivo noninvasively. Optical coherence tomography (OCT) was utilized in the functional imaging of optical cleaning agents for monitoring and quantifying the permeability coefficients (PCs) of them. Our experiments showed that the permeability coefficient of 40% propylene glycol from different subjects was averaged and found to be (2.52 ± 0.02) × 10−6 cm/s, the permeability coefficient of 40% glucose was (1.94 ± 0.05) × 10−6 cm/s, and the permeability coefficient of 40% glycerol was (1.82 ± 0.04) × 10−6 cm/s. The results indicated that the diffusion of propylene glycol solutions was faster than that of glucose solution, and the diffusion of glucose solutions was faster than that of glycerol solutions. The dependence of the permeability on the different hyperosmotic analytes could potentially be used in various basic science and clinical fields, such as optical clearing of tissues and cells as well as in clinical pharmacology.

In vitro study of ultrasound and different-concentration glycerol–induced changes in human skin optical attenuation assessed with optical coherence tomography

Previous studies have demonstrated the ultrasound-induced skin optical clearing enhancement with topical application of 60% glycerol (G) on in vitro porcine skin and in vivo human skin. Our purpose was to find the relation between the effect of optical skin clearing and different concentrations of glycerol and to find more effective ultrasound-glycerol combinations on optical skin clearing. The enhancement effect of ultrasound [Sonophoresis (SP) delivery] in combination with 40% G, 60% G, and 80% G on in vitro human skin optical clearing was investigated. Light imaging depths of skin were measured using optical coherence tomography. Different concentrations of glycerol and ultrasound with a frequency of 1 MHz and an intensity of 0.5 W/cm(2) was simultaneously applied for 15 min. The results show that with the increase of concentration of glycerol, the optical clearing of skin is much improved. Optical clearing capability of glycerol was more enhanced with simultaneous application of ultrasound compared with glycerol alone. The attenuation coefficients of skin tissues after application of 40% G/SP, 60% G/SP, and 80% G/SP decreased approximately 11.8%, 18.5%, and 20.0% at 15 min compared with 40% G, 60% G, and 80% G alone, respectively. The greatest decrease in attenuation coefficients at 60 min was approximately 52.3% and 63.4% for 80% G (without ultrasound) and 80% G/SP (with ultrasound), respectively, which are 2.1-fold and 2.6-fold to that in the 40% G.

Quantitative analysis on tongue inspection in traditional Chinese medicine using optical coherence tomography

Tongue inspection (TI) is an important and unique diagnostic method in traditional Chinese medicine (TCM), because significant connections between various viscerae diseases and abnormalities in the tongue have been verified. In TCM, TI is simple and non invasive, but in clinical applications, TI is subjectively based on the experience and technique of physicians. To avoid this problem, optical coherence tomography (OCT) imaging is introduced here for TI. We study OCT imaging in rats in vivo from chronic gastritis group (model) and normal group (control) and quantitatively analyze the relative parameters, such as the thickness and the moisture degree of TI. Our results show that OCT images properly demonstrate the thickness of the tongue coating and the moisture degree of the tongue in both groups, and the thickness is increased in the model group from that in the normal group, while the moisture degree decreases. As a result, OCT technology has the potential to provide physicians with an objective diagnostic standard for visual TI in TCM clinical practice and research.

Multifunctional Nanoplatform Based on Black Phosphorus Quantum Dots for Bioimaging and Photodynamic/Photothermal Synergistic Cancer Therapy

A multifunctional nanoplatform based on black phosphorus quantum dots (BPQDs) was developed for cancer bioimaging and combined photothermal therapy (PTT) and photodynamic therapy (PDT). BPQDs were functionalized with PEG chains to achieve improved biocompatibility and physiological stability. The as-prepared nanoparticles exhibite prominent near-infrared (NIR) photothermal and red-light-triggered photodynamic properties. The combined therapeutic application of PEGylated BPQDs were then performed in vitro and in vivo. The results demonstrate that the combined phototherapy significantly promote the therapeutic efficacy of cancer treatment in comparison with PTT or PDT alone. BPQDs could also serve as the loading platform for fluorescent molecules, allowing reliable imaging of cancer cells. In addition, the low cytotoxicity and negligible side effects to main organs were observed in toxicity experiments. The theranostic characteristics of PEGylated BPQDs provide an uplifting potential for the future clinical applications.

Synergistic effect of ultrasound and thiazone-PEG 400 on human skin optical clearing in vivo.

In this paper, we propose a new physical method in combination with mixed solution of thiazone and polyethylene glycol 400 (thiazone PEG 400 solution) penetration into tissue to assess the skin optical clearing. Four treatments were performed: (1) control group (C); (2) polyethylene glycol 400 (PEG400); (3) 0.25% thiazone (0.25%T); (4) 0.25% thiazone and 5‐min ultrasound (0.25%T/SP). The diffuse reflectance spectra and imaging depth of human skin in vivo at different times were measured by spectroscopy and optical coherence tomography (OCT). The optical clearing efficacy of skin was qualitatively and quantitatively analyzed. The results showed that the diffuse reflectance at 540 nm of samples at 10 min after being treated by 0.25%T/SP decreased by approximately 15.51%, whereas, 0.46%, 4.73% and 5.75% were received in C, PEG400 and 0.25%T, respectively. And at 60 min, the decrease in diffuse reflectance of samples in 0.25%T/SP is about 2.22‐fold, 1.20‐fold compared with that of the samples in PEG 400 and 0.25%T, at 540 nm, respectively. Simultaneously, 0.25%T/SP results in 41.33% increase in OCT 1/e light penetration depth after 60 min. There was a significant difference in the optical clearing effect on skin between ultrasound‐mixed solution of thiazone in combination with PEG 400 and the mixed solution (P < 0.05).

Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo-photothermal Therapy

In this work, novel theranostic platforms based on graphene oxide and AuNP core polyaniline shell (GO-Au@PANI) nanocomposites are fabricated for simultaneous SERS imaging and chemo-photothermal therapy. PANI, a new NIR photothermal therapy agent with strong NIR absorption, outstanding stability and low cytotoxicity is decorated on AuNPs by one-pot oxidative polymerization, then the Au@PANI core-shell nanoparticles are attached to the graphene oxide (GO) sheet via π-π stacking and electrostatic interaction. The obtained GO-Au@PANI nanohybirds exhibit excellent NIR photothermal transduction efficiency and ultrahigh drug-loading capacity. The nanocomposites can also serve as novel NIR SERS probes utilizing the intense SERS signals of PANI. Rapid SERS imaging of cancer cells is achieved using this ultrasensitive nanoprobe. GO-Au@PANI also reveals good capability of drug delivery with the DOX-loading efficiency of 189.2% and sensitive NIR/pH-responsive DOX release. The intracellular real-time drug release dynamics from the nanocomposites is monitored by SERS-fluorescence dual mode imaging. Finally, chemo-photothermal ablation of cancer cells is carried out in vitro and in vivo using GO-Au@PANI as high-performance chemo-photothermal therapeutic nanoagent. The theranostic applications of GO-Au@PANI endow it with great potential for personalized and precise cancer medicine.

Optical clearing of porcine skin tissue in vitro studied by Raman microspectroscopy

In present work, we studied the effect of optical clearing on porcine skin in vitro with glycerol by Raman microspectroscopy, denoted as RM, at various time intervals of 0, 15, 30, 45, 60, and 75 min respectively. The results showed that the addition of glycerol significantly improved the depth of RM measurement, and enhanced the recovery of skin tissue Raman spectra that were not overlapped with the glycerol Raman spectra over time. Moreover, it was found that the Raman signals resembled the native spectrum of the molecules in porcine skin with a negligible frequency shift. Furthermore, we evaluated the extent of optical clearing in porcine skin by utilizing various concentrations of 40%, 60%, and 80% glycerol solution. The results demonstrated that with the increase of concentration of glycerol, the optical clearing of porcine skin was much improved.

Potential ability of hematoporphyrin to enhance an optical coherence tomographic image of gastric cancer in vivo in mice

An ideal diagnostic system for the tumor tissues should be able to detect and define the location of tumor tissues and the early development of malignant diseases. There is great need for enhancement of imaging ability to tumor tissues. Optical coherence tomography (OCT) is used in detection and location of varied tumor tissues. In order to improve the sensitivity and specificity of an OCT image, hematoporphyrin as a new type of contrast agent was used in this study. The orthotopic graft model of gastric cancer in nude mice was used. The image formations of the tumor tissues without and with injection of hematoporphyrin in vivo were obtained by an OCT system at a 1,310 nm central wavelength. The experimental results showed that the tumor tissues accumulated with hematoporphyrin have an ability of light absorption which results in the increase of signal attenuation in the gastric cancer tissues, and that the boundary between the tumor tissues and surrounding normal tissues was perfectly defined owing to the accumulation of hematoporphyrin. From the experimental results, it is found that hematoporphyrin, a photosensitizing agent, could be used as a contrast agent for OCT imaging of tumor tissues, which offer an effective OCT image method for clinical detection and localization of tumor tissues in vivo.

Redox-responsive biodegradable PEGylated nanographene oxide for efficiently chemo-photothermal therapy: a comparative study with non-biodegradable PEGylated nanographene oxide.

Nanographene oxide (NGO) with a non-sheddable poly(ethylene glycol) (PEG) coating has been used for chemo-photothermal therapy. However, the drug release of PEGylated NGO (NGO-PEG) with an amine bond is adversely affected by the diffusion barrier effect of PEG shells. Here, we developed a simple new method for the preparation of biodegradable PEGylated NGO conjugates (NGO-SS-PEG) with cleavable disulfide bonds for rapid drug release and more efficiently chemo-photothermal therapy. The glutathione (GSH)-induced and photothermal-mediated intracellular release of doxorubicin (DOX) from NGO-SS-PEG was studied in A549 cells using confocal laser scanning microscopy and flow cytometry analysis. In vivo cytotoxicity experiments were performed on chemo-photothermal therapy. Furthermore, we presented a comparative study of intracellular drug release and biological efficacy between NGO-SS-PEG/DOX and NGO-PEG/DOX. The results demonstrated that the rapid drug release from the NGO-SS-PEG conjugates with sheddable PEG was triggered upon the stimulus of high GSH levels inside A549 cells. Interesting, the DOX release mediated by the photothermal effect from the NGO-SS-PEG conjugates was found to be more obvious than that for NGO-PEG. Additionally, NGO-SS-PEG showed a higher efficacy than NGO-PEG for anti-tumor therapy compared with NGO-PEG. Thus, NGO-SS-PEG can improve therapeutic efficacy and is an attractive drug nanocarrier.