(334a) Transformable Liquid-Metal Nanomedicine

TRANSFORMABLE
LIQUID-METAL NANOMEDICINE

Yue Lu^1,2, Quanyin Hu^1,2,
Yiliang Lin², Frances S. Ligler^1,2, Michael D. Dickey²
and Zhen Gu^1,2,*

¹ University of North Carolina at Chapel Hill, Chapel Hill, NC,
27599, USA;

² North Carolina State University, Raleigh, NC, 27695, USA

Purpose

     To date,
numerous inorganic nanocarriers have been explored for drug delivery systems
(DDSs). However, the clinical application of inorganic formulations has often
been hindered by their toxicity and failure to biodegrade. We report here a
novel liquid metal (eutectic alloy of gallium indium, designated EGaIn)-based
nano-scale formulation for controlled drug delivery to achieve enhanced
anticancer therapy.

Methods

     To obtain
liquid-metal based drug nanocarriers, an ¡°emulsion¡±-like ligand-mediated
procedure is simply applied through ultrasonication at room temperature. During
sonication, the thiolated ligands readily assemble onto the surface of the
EGaIn, competing with the oxidation process and facilitating control of the
particle size. The two ligands used here, thiolated (2-hydroxypropyl)-¦Â-cyclodextrin
and thiolated hyaluronic acid, not only serve as capping agents during the
formation of nano-scaled liquid-metal spheres, but also play roles of drug
loading matrix and active targeting moiety, respectively. The final formulation
(designated LM-NP/L) comprises three primary functional constituents: a cyclodextrin-based
drug loading motif, the targeting ligand hyaluronic acid and an EGaIn core.

Results

     The resulting
nanoparticles loaded with Dox have an average diameter of 107 nm and
demonstrate the capability to fuse and subsequently degrade under a mildly
acidic condition, which facilitates release of Dox in acidic endosomes after
cellular internalization. Equipped with hyaluronic acid, a tumour-targeting
ligand, this formulation displays enhanced chemotherapeutic inhibition toward
the xenograft tumour-bearing mice. This metal-based DDS with fusible and
degradable behavior under physiological conditions provides a new strategy for
engineering theranostic agents with low toxicity.

Figure 1. Schematic design and TEM
image.

Figure 2. In vivo antitumour
efficacy.

Conclusions

     We have
developed a new liquid metal-based drug delivery platform for anticancer
therapy. The formulation can be easily formed and tailored via
ligand-mediated self-assembly using facile ultrasonication. The resulting
liquid-metal nanospheres are able to fuse for promoting drug release and
eventually degrade under a mild acidic environment. After fusing, these
nanospheres also display a contrast enhancing capability when imaged by X-ray,
suggesting potential as a theranostic reagent. Systematic investigation of
toxicology of LM-NP/L revealed no obvious toxicity at the treatment
dose, favoring its biomedical applications.

Acknowledgements: NIH (CTSA, 1UL1TR001111) and NSF (CMMI-0954321,
DMR-1121107).

References:

1.    Yue Lu, Quanyin Hu, Yiliang Lin, Dennis
B. Pacardo, Chao Wang, Wujin Sun, Frances S. Ligler, Michael D. Dickey and Zhen
Gu (2015), ¡°Transformable Liquid-metal Nanomedicine,¡± Nature Communications, 6,
10066.