Zhouyi Guo

Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide

Graphene has shown great potential both in photothermal therapy and drug delivery. Herein, we developed doxorubicin-loaded PEGylated nanographene oxide (NGO-PEG-DOX) to facilitate combined chemotherapy and photothermal therapy in one system. In this work, we studied the ablation of tumor both in vivo and in vitro by the combination of photothermal therapy and chemotherapy using this functional graphene oxide. The ability of the NGO-PEG-DOX nanoparticle to combine the local specific chemotherapy with external near-infrared (NIR) photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with chemotherapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy. Furthermore, lower systematic toxicity of NGO-PEG-DOX than DOX was proved by the pathologic examination of main organs in our toxicity study.

Folic acid-conjugated graphene oxide for cancer targeted chemo-photothermal therapy.

Nanographene oxide (NGO), a new type of nanomaterial for anticancer drugs delivery and near-infrared (NIR)-mediated photothermal ablation of tumors, has been used in the combination of photothermal therapy and chemotherapy. Herein, targeted chemo-photothermal therapy based on polyvinylpyrrolidone (PVP) functionalized NGO was achieved. Folic acid (FA), a common target molecule to cancer cells, was conjugated to NGO via covalent amide bond. The obtained FA-NGO-PVP was proved to be an ideal pH-responsive nanocarrier for delivery of an anticancer drug doxorubicin (DOX) with the loading ratio more than 100%. In vitro experiments were then performed with the combination of chemotherapy and NIR photothermal therapy. The results demonstrated that the targeted chemo-photothermal therapy could specifically deliver drug and heat to tumor sites and showed excellent efficacy of anticancer therapy. Thus, FA-NGO-PVP could be used as a novel nanomaterial for selective chemo-photothermal therapy.

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.

Noninvasive prostate cancer screening based on serum surface-enhanced Raman spectroscopy and support vector machine

This study aims to present a noninvasive prostate cancer screening methods using serum surface-enhanced Raman scattering (SERS) and support vector machine (SVM) techniques through peripheral blood sample. SERS measurements are performed using serum samples from 93 prostate cancer patients and 68 healthy volunteers by silver nanoparticles. Three types of kernel functions including linear, polynomial, and Gaussian radial basis function (RBF) are employed to build SVM diagnostic models for classifying measured SERS spectra. For comparably evaluating the performance of SVM classification models, the standard multivariate statistic analysis method of principal component analysis (PCA) is also applied to classify the same datasets. The study results show that for the RBF kernel SVM diagnostic model, the diagnostic accuracy of 98.1% is acquired, which is superior to the results of 91.3% obtained from PCA methods. The receiver operating characteristic curve of diagnostic models further confirm above research results. This study demonstrates that label-free serum SERS analysis technique combined with SVM diagnostic algorithm has great potential for noninvasive prostate cancer screening.

Rapid Intracellular Growth of Gold Nanostructures Assisted by Functionalized Graphene Oxide and Its Application for Surface-Enhanced Raman Spectroscopy

Hybridization of metal nanoparticles with graphene oxide for high performance surface-enhanced Raman scattering (SERS) has attracted overwhelming attention in recent years. Herein, a one-pot green route for intracellular synthesis of gold nanostructures assisted by poly(vinylpyrrolidone) (PVP)-functionalized graphene oxide (GO) was proposed. The hybrids obtained [GO/PVP/intracellularly grown gold nanoparticles (IGAuNs)] randomly scattered throughout the cell. Compared with the IGAuNs, the growth of GO/PVP/IGAuNs was remarkably accelerated, which could be attributed to the coordination of PVP enriched on GO. GO/PVP/IGAuNs could serve as excellent SERS probes for ultrasensitive detection of cellular components of cancer cells located in the cytoplasm, nucleoplasm, and nucleolus. The random intracellular distribution of GO/PVP/IGAuNs facilitated the effective Raman characterization of cellular components, which was confirmed by the uniform distribution of SERS signals in the Raman image. The SERS signals induced by GO/PVP/IGAuNs could be collected as early as 15 h, which allowed rapid detection of tumor cells. In conclusion, this facile and green strategy for fast intracellular growth of GO/PVP/IGAuNs offered great potential for biomedical applications.

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.

Study of support vector machine and serum surface-enhanced Raman spectroscopy for noninvasive esophageal cancer detection

Abstract. The ability of combining serum surface-enhanced Raman spectroscopy (SERS) with support vector machine (SVM) for improving classification esophageal cancer patients from normal volunteers is investigated. Two groups of serum SERS spectra based on silver nanoparticles (AgNPs) are obtained: one group from patients with pathologically confirmed esophageal cancer (n=30) and the other group from healthy volunteers (n=31). Principal components analysis (PCA), conventional SVM (C-SVM) and conventional SVM combination with PCA (PCA-SVM) methods are implemented to classify the same spectral dataset. Results show that a diagnostic accuracy of 77.0% is acquired for PCA technique, while diagnostic accuracies of 83.6% and 85.2% are obtained for C-SVM and PCA-SVM methods based on radial basis functions (RBF) models. The results prove that RBF SVM models are superior to PCA algorithm in classification serum SERS spectra. The study demonstrates that serum SERS in combination with SVM technique has great potential to provide an effective and accurate diagnostic schema for noninvasive detection of esophageal cancer.

Study of molecule variations in renal tumor based on confocal micro-Raman spectroscopy

Abstract. Confocal micro-Raman spectroscopy—a valuable analytical tool in biological and medical field of research—allows probing molecular vibrations of samples without external labels or extensive preparation. We employ confocal micro-Raman spectroscopy to characterize renal tumors and normal tissue. Results show that Raman peaks of the renal tumor at 788 and 1087  cm−1, which belong to νsPO2− and νasPO2− stretching, respectively, have an obvious increase. At the same time, the ratio of I855/I831 in renal tumor tissue is 1.39±0.08, while that in normal renal tissue is 2.44±0.05 (p<0.01). This means that more tyrosine conformation transform from “buried” to “exposed” in the presence of cancer. Principal component analysis is used to classify the Raman spectra of renal tumor tissue and normal tissue.

Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481–486, 682–687, 1018–1034, 1313–1323, 1450–1459 and 1582–1587 cm−1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.