Liquid metal-based nano-terminators enhance anti-cancer therapy

Liquid metal-based nano-terminators can enhance anti-cancer therapy

8:57 AM, 19th July 2016
Liquid metal-based nano-terminators can enhance anti-cancer therapy
Yue Lu and Zhen Gu, professor & assistant professor respectively, joint biomedical engineering department in the North Carolina State University (NC State) and University of North Carolina at Chapel Hill (UNC-CH).

In an interaction Yue Lu and Zhen Gu, professor & assistant professor respectively, joint biomedical engineering department in the North Carolina State University (NC State) and University of North Carolina at Chapel Hill (UNC-CH) with Chemical Today magazine describes about the path breaking research in which gallium indium alloy- used as a liquid-metal nanocarrier holds the key not just for effective anti-cancer treatment but for a wide range of therapeutics.

Tell us about your current research work.

Our research laboratory is interest­ed in exploring novel strategies that apply stimuli-responsive systems for delivering therapeutics in dose-, spatial- and temporal controlled fashions. By accumulating and integrating tools of biomolecular engineering, materials chemistry and micro/nano fabrication, we are adapting the concept of “artificial vesicles”, which are inspired by ef­fective approaches found in natural particulates, from viruses to cells.

Drug delivery through such vehicles can be specifically regulated by physiological signals, such as glu­cose, ATP and reactive oxygen spe­cies, the level or activity of which is often closely associated with many diseases, including diabetes and cancer. In particular, we are studying glucose-responsive syn­thetic formulations and devices for delivering insulin in a self-regulated manner, which mimics the function of pancreatic β-cells. We are also developing the “programmed” anti­cancer drug delivery systems that can respond upon the elements within tumor microenvironment or subcellular environment and sequentially release multiple drugs to their most active destinations. In addition to endogenous triggers, we are also interested in utilizing exog­enous triggers, such as ultrasound and light to achieve spatiotemporal administration.

In this particular work, we devel­oped a novel liquid metal-based nano-scale formulation (the na­no-terminators) for drug delivery to achieve enhanced anticancer therapy. Taking advantage of the unique characteristics of a gallium-indium alloy, this nanomedicine has a variety of advantages in term of simple fabrication, facile surface bioconjugation, and the capability of fusion and degradation in a mild­ly acidic environment. It should be noted that the liquid-metal nano­carrier itself displayed low system­atic toxicity, favoring it biomedical applications.

Explain about biodegrad­able liquid metals carriers / nano-terminators that have been used for drug delivery

The nano-terminator is a core-shell nanosphere composed of a liquid-phase gallium-indium alloy core and a thiolated polymeric shell. This formulation can be simply produced through a sonication-me­diated method with bioconjugation flexibility.

The resulting doxorubicin (Dox, a broad-spectrum anticancer drug) loaded nanoparticles 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 drug delivery system with fusible and degradable behavior under physiological con­ditions provides a new strategy for engineering theranostic agents with low toxicity.

How do you create these nano-terminators?

To create the nano-terminators, we place the bulk liquid metal (gallium-indium alloy) into a solution that contains two types of polymeric ligands. The solution is then hit with ultrasound, which forces the bulk liquid metal to burst into nanoscale droplets approximately 100 nano­meters in diameter. The ligands in the solution attach to the surface of the droplets as they break away from the bulk liquid metal.

How important is gallium-indium alloy in this whole process as a bulk material?

The bulk material we use here is gallium-indium alloy. It is a low-vis­cosity liquid at room temperature, just like mercury, which makes it a suitable candidate for nanofabrica­tion. Unlike mercury, it has low-tox­icity, thus is promising in biomedical applications.

What is the role of polymeric ligands in finding cancer cells?

One of the ligands is chemically modified hyaluronic acid. It sup­ports active tumour-targeting to­ward the receptors over expressed on the cell surface of a broad variety of tumours.

What challenges did you face during your research?

The engineering flexibility provided by inorganic nanoparticles with tailor able shape, size, surface ligands and physical properties has enabled on-demand design of nov­el drug delivery systems, contrast agents, and integrated systems for disease diagnosis and treatment. The last decade has witnessed numerous efforts in developing inorganic nanoparticles capable of effectively targeting different diseases. However, these formula­tions often fail to be useable due to systemic toxicity.

For instance, targeted cancer therapy requires nanoparticles with relatively large sizes to minimize clearance and enhance tumour retention, yet such inorganic par­ticles often remain in the body for a long time because of their lack in biodegradability. To date, few studies have demonstrated how to engineer the physicochemical prop­erties of inorganic nanoparticles to satisfy both target delivery and efficient elimination. This design bottleneck has long existed and is impeding the clinical translation of therapy and diagnostics based on inorganic carriers.

Mention some of the other important applications and uses for your research work?

The nano-terminator can help the doctors locate tumours as well as anticancer treatment. It should also be pointed out that this technique can be used with a wide range of therapeutics (and it’s not necessari­ly limited to anticancer agents).

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See the Interview Coverage in Chemical Today magazine (Pg 48)

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