Tag Archives: Xianlin Zheng

New nanoparticles help detect deep-tissue cancers

6 August 2018:

Researchers have developed a new form of nanoparticle and associated imaging technique that can detect multiple disease biomarkers, including those for breast cancer, found in deep-tissue in the body.

Reported in the science journal ‘Nature Nanotechnology’, the research opens up a new avenue in minimally invasive disease diagnosis and will potentially have widespread use both for biomedical research and for clinical applications.

“The use of nanoparticles for bio-imaging of disease is an exciting and fast-moving area of science,” says research author Dr Yiqing Lu (pictured) at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University.

“Specially designed nanoparticles can be placed in biological samples or injected into specific sites of the body and then ‘excited’ by introduced light such as that from a laser or an optical fibre,” he says.

“Disease biomarkers targeted by these nanoparticles then reveal themselves, by emitting their own specific wavelength signatures which are able to be identified and imaged.”

A major limitation however is that only a single disease biomarker at a time is able to be distinguished and quantified in the body using this type of detection technique.

“Detection of multiple biomarkers (known as multiplexing) in the body has been a major challenge for researchers,” says Dr Lu.

“The tissue environment is extremely complex—full of light absorbing and scattering elements such as blood, muscle and cartilage. And introducing multiple nanoparticles to a site, operating at multiple wavelengths to detect multiple biomarkers, produces too much interference. It makes it extremely difficult to determine accurately if a range of disease biomarkers are present.”

What Dr Lu and the research team have done to solve this issue has been to engineer innovative nanoparticles that emit light at the same frequency (near infrared light) but that are able to be coded to emit light for set periods of time (in the microsecond-to-millisecond time range).

“It is the duration of the light-emission and the biomarker reaction to this timed amount of light (known as luminescence lifetime) that produces a clearly identifiable molecular signature,” he says.

“Multiple disease biomarkers can be clearly identified and imaged based on this approach as there are no overlapping wavelengths interfering with the reading.”

“This enables high-contrast optical biomedical imaging that can detect multiple disease biomarkers all at the one time.” says Dr Lu.

In an exciting breakthrough in laboratory testing, the innovative nanoparticles have been able to detect multiple forms of breast cancer tumours in mice.

“We’re extremely excited where this work is taking us,” says Professor Fan Zhang at Fudan University (China) and joint-lead author on the research publication.

“We were able to successfully detect and identify key biomarkers for a number of different sub-types of breast cancer.”

“This technique has the potential to provide a low-invasive method of determining if breast cancer is present, as well as the form of breast cancer, without the need to take tissue samples via biopsy.”

“Ultimately our novel nanoparticles will enable quantitative assessment for a wide range of disease and cancer biomarkers, all at one time. The technique will be able to be used for early-stage disease screening and potentially utilised in integrated therapy,” says Professor Fan Zhang.

Professor Jim Piper, CNBP node leader at Macquarie University and also an author on the paper is similarly upbeat with the results that have been obtained.

“This is a major advance in a long-term effort at our Centre at Macquarie University to develop innovative techniques for simultaneous detection of multiple disease markers in humans and animals,” he says.

“Next steps in our research collaboration are to further refine the nanoparticles, to examine issues related to a clinical roll-out of the technology and to explore further applications and disease areas where this technique could be best utilised.”

Reported in the prestigious journal ‘Nature Nanotechnology’, the international team of researchers involved with the study are based at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University and Fudan University, China.

Notably, the work is an extension of previous nanoparticle-imaging research undertaken by Dr Lu at Macquarie University which has been awarded a patent in the United States and China, and which has already been licensed with commercial partners.

Journal: Nature Nanotechnology.

Publication title: Lifetime-engineered NIR-II nanoparticles unlock multiplexed in vivo imaging.

Authors: Yong Fan, Peiyuan Wang, Yiqing Lu, Rui Wang, Lei Zhou, Xianlin Zheng, Xiaomin Li, James A. Piper & Fan Zhang.

Below: A stylised image of cancer detecting nanoparticles in the body. Credit: Yong Fan.

Paper published in Analytical Chemistry

Xianlin Zheng_web125 February 2016:

CNBP researchers have published a paper in the journal Analytical Chemistry titled, “High-contrast visualization of upconversion luminescence in mice using timegating approach.”

Authors: Xianlin Zheng, Xingjun Zhu, Yiqing Lu, Jiangbo Zhao, Wei Feng, Guohua Jia, Fan Wang, Fuyou Li and Dayong Jin.

Abstract: Optical imaging through the near-infrared (NIR) window provides deep penetration of light up to several centimetres into biological tissues. Capable of emitting 800-nm luminescence under 980-nm illumination, the recently-developed upconversion nanoparticles (UCNPs) suggest a promising optical contrast agent for in vivo bioimaging. However, presently they require high-power lasers to excite when applied to small animals, leading to significant scattering background that limits the detection sensitivity as well as detrimental thermal effect. In this work, we show that the time-gating approach implementing pulsed illumination from a NIR diode laser and time-delayed imaging synchronized via an optical chopper offers detection sensitivity more than one order of magnitude higher than the conventional approach using optical band-pass filters (S/N: 47321/6353 vs. 5339/58), when imaging UNCPs injected into Kunming mice. The pulsed laser illumination (70μs ON in 200 μs period) also reduces the overall thermal accumulation to 35% of that under the continuous-wave mode. Technical details are given on setting up the time-gating unit comprising an optical chopper, a pinhole and a microscopy eyepiece. Being generally compatible with any cameras, this provides a convenient and low cost solution to NIR animal imaging using UCNPs as well as other luminescent probes.

The full paper is accessible online.

 

In-vivo imaging of Vitamin C

Dayong Jin  Low Res Edit 009618 September 2015:

A new paper has been released in Scientific Reports with two CNBP researchers as contributing authors –  Dayong Jin and Xianlin Zheng. The paper detailed the successfull development of a responsive luminescence probe, TOB-Eu3+, for specific recognition and background-free quantification of vitamin C in living cells and lab animals.

Authors: Bo Song, Zhiqing Ye, Yajie Yang, Hua Ma, Xianlin Zheng, Dayong Jin & Jingli Yuan

Abstract: Sensitive optical imaging of active biomolecules in the living organism requires both a molecular probe specifically responsive to the target and a high-contrast approach to remove the background interference from autofluorescence and light scatterings. Here, a responsive probe for ascorbic acid (vitamin C) has been developed by conjugating two nitroxide radicals with a long-lived luminescent europium complex. The nitroxide radical withholds the probe on its “off” state (barely luminescent), until the presence of vitamin C will switch on the probe by forming its hydroxylamine derivative. The probe showed a linear response to vitamin C concentration with a detection limit of 9.1 nM, two orders of magnitude lower than that achieved using electrochemical methods. Time-gated luminescence microscopy (TGLM) method has further enabled real-time, specific and background-free monitoring of cellular uptake or endogenous production of vitamin C, and mapping of vitamin C in living Daphnia magna. This work suggests a rational design of lanthanide complexes for background-free small animal imaging of biologically functional molecules.

The full paper is accessible online.

CNBP represented at CYTO 2015

Yiqing Lu27 June 2015:

Associate Investigator Dr Yiqing Lu and PhD student Mr Xianlin Zheng were CNBP attendees at CYTO 2015 – the 30th Congress of the International Society for Advancement of Cytometry held in Glasgow, June 26-30, 2015.

Oral presentations were given by both – ‘A Multifunction Workstation Underpinning Lanthanide-Based Luminescence Techniques’ by Dr Lu and ‘Precise Pinpointing of Luminescent Targets Empowers Quantitative Scanning Cytometry’ by Mr Zheng.

Dr Lu was also on the program committee.

While in the UK, both researchers took the time to visit CNBP Partner Prof Tong Sun at City University London, as well as Prof Klaus Suhling at King’s College London and Prof Peter Sadler at the University of Warwick.

Student travel grant awarded

Xianlin Zheng28 April 2015:

Congratulations to Xianlin Zheng, a Centre PhD student, who has been selected as a recipient of the 2015 Student Travel Award for attendance at CYTO 2015 (The International Society for Advancement of Cytometry’s 30th International Congress). The event is to be held at the Scottish Exhibition and Conference Centre in Glasgow, Scotland and the grant has a value of US$1000.