Yun Liu, Anton P.J. Middelberg, Chun-Xia Zhao*

 

Australian Institute for Bioengineering and Nanotechnology
 The University of Queensland
Brisbane, Queensland, Australia

 

Nanotechnology holds great promise for cancer drug delivery.  The FDA approved Poly Lactic-co-Glycolic Acid (PLGA) is one of the most promising polymeric nanocarriers for targeted drug delivery because of its excellent biodegradability and biocompatibility. For single-ligand targeted drug delivery, receptors that bind with targeting ligands on the nanoparticle surface are generally not exclusively over-expressed on cancer cells, resulting in compromised targeting efficiency. Compared to the single-ligand strategy, the dual-ligand approach is a promising strategy to produce synergistic targeting effects, and enhance specific cellular uptake. This work reports the synthesis of a combinatorial library of single and dual-ligand PLGA nanoparticles loaded with an imaging agent using a simple one-step microfluidic method. This microfluidic method offers rapid mixing, precise control over particle size, size distribution, surface charge, ligand density, and the ratio of different ligands, which is usually extremely difficult to achieve by using traditional “beaker methods”. To achieve the optimum targeting specificity, plain, single-ligand and dual-ligand PLGA nanoparticles (i.e., folic acid and hydraulic acid) with the ligand density and ligand ratios systematically varied were fabricated and screened using both 2D monolayer cells models and 3D tumor spheroid models. The optimal dual-ligand PLGA nanoparticle formulation demonstrated negligible uptake for macrophage and receptor negative cell, but significantly enhanced the uptake of receptors positive cell (having receptors for both ligands) in the monolayer cellular uptake experiments among all formulations. Similarly, the optimal formulation also achieved the best synergetic targeting efficacy in the 3D tumor spheroid model.

 

Biographic Details

Yun Liu

Title: PhD student

Affiliation, Country: Australian Institute for Bioengineering and Nanotechnology, Australia

Phone: +61424091600 E-mail: yun.liu2@uq.net.au

Research interests: nanomedicine, drug delivery, polymeric nanoparticle

Venue

Room: 
Hawken N201