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1.  In vivo Pulsed Magneto-motive Ultrasound Imaging Using High-performance Magnetoactive Contrast Nanoagents 
Nanoscale  2013;5(22):11179-11186.
Previously, pulsed magneto-motive ultrasound (pMMUS) imaging has been introduced as a contrast-agent-assisted ultrasound-based imaging modality capable of visualizing biological events at the cellular and molecular level. In pMMUS imaging, a high intensity pulsed magnetic field is used to excite cells or tissue labeled with magnetic nanoparticles. Then, ultrasound (US) imaging is used to monitor the mechanical response of the tissue to an externally applied magnetic field (i.e., tissue displacement). Signal to noise ratio (SNR) in pMMUS imaging can be improved by using superparamagnetic nanoparticles with larger saturation magnetization. Metal-doped magnetic nanoparticles with enhanced tunable nanomagnetism are suitable candidates to improve the SNR and, therefore, sensitivity of pMMUS imaging, which is essential for in vivo pMMUS imaging. In this study, we demonstrate the capability of pMMUS imaging to identify the presence and distribution of zinc-doped iron oxide nanoparticles in live nude mice bearing A431 (human epithelial carcinoma) xenograft tumors.
doi:10.1039/c3nr03669c
PMCID: PMC3916332  PMID: 24080913
2.  Current early diagnostic biomarkers of prostate cancer 
Asian Journal of Andrology  2014;16(4):549-554.
Prostate cancer (PCa) has become to have the highest incidence and the second mortality rate in western countries, affecting men's health to a large extent. Although prostate-specific antigen (PSA) was discovered to help diagnose the cancer in an early stage for decades, its specificity is relative low, resulting in unnecessary biopsy for healthy people and over-treatment for patients. Thus, it is imperative to identify more and more effective biomarkers for early diagnosis of PCa in order to distinguish patients from healthy populations, which helps guide an early treatment to lower disease-related mortality by noninvasive or minimal invasive approaches. This review generally describes the current early diagnostic biomarkers of PCa in addition to PSA and summarizes the advantages and disadvantages of these biomarkers.
doi:10.4103/1008-682X.129211
PMCID: PMC4104079  PMID: 24830695
early diagnostic biomarkers; MALAT1-derived miniRNA; PCA3; prostate cancer; PSA
3.  Contrast-enhanced magneto-photo-acoustic imaging in vivo using dual-contrast nanoparticles☆ 
Photoacoustics  2014;2(2):55-62.
By mapping the distribution of targeted plasmonic nanoparticles (NPs), photoacoustic (PA) imaging offers the potential to detect the pathologies in the early stages. However, optical absorption of the endogenous chromophores in the background tissue significantly reduces the contrast resolution of photoacoustic imaging. Previously, we introduced MPA imaging – a synergistic combination of magneto-motive ultrasound (MMUS) and PA imaging, and demonstrated MPA contrast enhancement using cell culture studies. In the current study, contrast enhancement was investigated in vivo using the magneto-photo-acoustic (MPA) imaging augmented with dual-contrast nanoparticles. Liposomal nanoparticles (LNPs) possessing both optical absorption and magnetic properties were injected into a murine tumor model. First, photoacoustic signals were generated from both the endogenous absorbers in the tissue and the liposomal nanoparticles in the tumor. Then, given significant differences in magnetic properties of tissue and LNPs, the magnetic response of LNPs (i.e. MMUS signal) was utilized to suppress the unwanted PA signals from the background tissue thus improving the PA imaging contrast. In this study, we demonstrated the 3D MPA imaging of LNP-labeled xenografted tumor in a live animal. Compared to conventional PA imaging, the MPA imaging show significantly enhanced contrast between the nanoparticle-labeled tumor and the background tissue. Our results suggest the feasibility of MPA imaging for high contrast in vivo mapping of dual-contrast nanoparticles.
doi:10.1016/j.pacs.2013.12.003
PMCID: PMC3956135  PMID: 24653976
PA, photoacoustic; MMUS, magneto-motive ultrasound; MPA, magneto-photo-acoustic; NPs, nanoparticles; LNPs, liposomal nanoparticles; Contrast enhancement; Magneto-photoacoustic imaging; Nanoparticle distribution; Dual-contrast nanoparticles
4.  Investigating intratumour heterogeneity by single-cell sequencing 
Asian Journal of Andrology  2013;15(6):729-734.
Intratumour heterogeneity is a longstanding field of focus for both researchers and clinicians. It refers to the diversity amongst cells within the same tumour. Two major hypotheses have attempted to explain the existence of intratumour heterogeneity: (i) the clonal evolution (CE) theory and (ii) the cancer stem cell (CSC) model. CE theory emphasizes the evolutionary biological characteristics of the tumour, underscoring the initiation and progression of the disease. In contrast, the CSC model focuses on stem cell differentiation into distinct functions in order to stabilize the tumour microenvironment. Here we consider single-cell sequencing (SCS) as a newly developed technique for application to the investigation of intratumour heterogeneity and assess its relevance within research and clinical environments. Early detection of rare tumour cells, monitoring of circulating tumour cells (CTCs) and control of the occurrence of drug resistance are important goals in early diagnosis, prognosis prediction and individualized medicine.
doi:10.1038/aja.2013.106
PMCID: PMC3854033  PMID: 24141534
clinical applications; intratumour heterogeneity; single-cell sequencing
5.  Pulsed magneto-motive ultrasound imaging to detect intracellular trafficking of magnetic nanoparticles 
Nanotechnology  2011;22(41):415105.
As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular trafficking of nanoparticles – an important part of cell-nanoparticle interaction, has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique – pulsed magneto-motive ultrasound (pMMUS), to identify intracellular trafficking of endocytosed magnetic nanoparticles. In pulsed magneto-motive ultrasound imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e. intracellular aggregation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular trafficking non-invasively and in real-time.
doi:10.1088/0957-4484/22/41/415105
PMCID: PMC3471148  PMID: 21926454
Pulsed magneto-motive ultrasound imaging; superparamagnetic iron-oxide nanoparticles; macrophage; endocytosis; intracellular trafficking
6.  Magneto-photo-acoustic imaging 
Biomedical Optics Express  2011;2(2):385-396.
Magneto-photo-acoustic imaging, a technique based on the synergy of magneto-motive ultrasound, photoacoustic and ultrasound imaging, is introduced. Hybrid nanoconstructs, liposomes encapsulating gold nanorods and iron oxide nanoparticles, were used as a dual-contrast agent for magneto-photo-acoustic imaging. Tissue-mimicking phantom and macrophage cells embedded in ex vivo porcine tissue were used to demonstrate that magneto-photo-acoustic imaging is capable of visualizing the location of cells or tissues labeled with dual-contrast nanoparticles with sufficient contrast, excellent contrast resolution and high spatial resolution in the context of the anatomical structure of the surrounding tissues. Therefore, magneto-photo-acoustic imaging is capable of identifying the nanoparticle-labeled pathological regions from the normal tissue, providing a promising platform to noninvasively diagnose and characterize pathologies.
doi:10.1364/BOE.2.000386
PMCID: PMC3038453  PMID: 21339883
(170.5120) Photoacoustic imaging; (110.7170) Ultrasound; (170.3880) Medical and biological imaging; (170.6960) Tomography

Results 1-6 (6)