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AIBN SEMINAR SERIES 2012:

 

Presenter:

Associate Professor Gordon Xu, Associate AIBN Group Leader

Title:

Biomedical Applications of Layered Double Hydroxide Nanoparticles

Date:

Friday, 12 October 2012

Time:

12:00pm

Venue:

Physiology Lecture Theatres (Building 63) – Lecture Theatre 360

 

Abstract:  Layered double hydroxides (LDHs), also known as anionic clays, find a high potential in nanomedicinal application as the drug/gene delivery vehicle. These nanomaterials show a number of advantages over the counter-part organic ones, such as easy preparation in lab at low cost, precise control in particle size, low cytotoxicity, good biocompatibility, and high endosomal escapability. We have developed a robust way to control prepare LDH nanoaprticles (NPs) with the particle size of 30-300 nm in a stable homogeneous suspension.

 

We have first found that LDH NPs can be quickly taken up by various cell lines, in a clathrin-mediated dose-dependent and time-dependent endocytosis pathway. More excitedly, we have for the first time discovered that the rod-like LDH NPs are mostly located in the nucleus while plate-like LDH NPs in the perinuclear area, which may imply a strategy that can be used to target the subcellular compartments by controlling the shape/size of delivery vehicles.

 

We have then found that LDH NPs can deliver supercoiled plasmid DNA (ca. 6.1k bps) into various cell lines with a transfection efficacy up to 70-80% cells in the optimized conditions.  Moreover, LDH NPs are able to siRNA into CHO cells to knockdown the expression of the target protein with the efficiency compared with the commercial delivery vehicle. We have shown that cultured neurons can more efficiently internalize siRNA-LDH NPs than non-neuronal cells (eg. fibroblasts), and that release of siRNA into the neuronal cytoplasm resulted in knockdown of the axon guidance receptor DCC.

 

We have also found that LDH NPs are able to deliver anti-restenotic drug, low molecular weight heparin (LMWH) to vascular smooth muscle cells (SMCs). Intercalation of LMWH into LDH enables the release to sustain for over 5 days. LMWH-LDH nanohybrids enhance the inhibition to SMC proliferation and migration by ~60% compared with the control, e.g. promoting the biological functions of LMWH on SMCs, which is actively pursued for anti-restenosis treatment.

 

Very recently, we have found for the first time that LDH can be used as a good antigen carrier for effective promotion of the antibody response. The activity of LDH nanoparticles is even higher than the commonly used adjuvant QuilA. More works are underway.

 

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