Title: Engineering clay nanoparticles as activatable MR imaging contrast agent for accurate tumour detection

Speaker: Dr. Zi (Sophia) Gu

School of Chemical Engineering

University of New South Wales, Sydney, Australia

Time: 2018年5月24日星期四上午10:00-11:00

Venue: 放射医学与防护学院 401号楼一楼1125会议室

ABSTRACT:

Magnetic resonance (MR) imaging is currently one of the most powerful non-invasive molecular imaging techniques for cancer diagnosis, providing anatomical images of tissues and organs with excellent spatial resolutions. The diagnostic capabilities of MR imaging can be greatly improved by introducing exogenous contrast agents (T1 or T2 weighted contrast agents) to enhance target tissue contrast by altering the relaxation time of nearby water protons. We recently developed a novel manganese-containing layered double hydroxide (Mn-LDH) nanoparticle that demonstrated clear and enhanced T1-weighted MR imaging of tumour tissues in mice by intravenous injection. The Mn-LDH contrast agent exhibited superb T1-weighted relaxivity (2.8 fold of commercial gadolinium chelates) and ultrasensitive response to the mildly acidic tumour microenvironment (relaxivity = 7.6 mM-1s-1 at pH 6.5, compared with 1.16 mM-1s-1 at pH 7.4), indicating the activatable OFF/ON contrast effect in normal tissue/tumour tissue. The mechanism for ultrasensitive pH response and high relaxivity was revealed to be enhanced water exchange caused by the microstructure change of Mn-LDH nanoparticles in the tumour microenvironment.

Based on the findings with Mn-LDH, a T1-T2 dual-mode MR imaging contrast agent was fabricated by integrating Mn-LDH and superparamagnetic iron oxide (IO) nanoparticles into a single MnLDH-IO nanoparticle. The MnLDH-IO dual-mode contrast agent demonstrated significantly higher relaxivity under mildly acidic conditions (replicating the pH of the tumour microenvironment) than at pH 7.4 (normal tissue pH). The T1 and T2 weighted relaxivity of MnLDH-IO nanoparticles were 2.1 and 1.1 fold of T1 weighted relaxivity of Mn-LDH and T2 weighted relaxivity of IO respectively, which demonstrated that their contrast effect maintained the same or even increased compared with the single mode components, without the interference effect. The intratumoural or intravenous injection of MnLDH-IO nanoparticles exhibited clear dual-mode (T1 and T2 weighted) MR imaging of tumour tissues in breast tumour bearing mice.