# Design Principles for Engineering Ionic Liquid-Gold Nanoparticles for Therapeutic Delivery to the Brain

## TL;DR

This paper outlines design principles for creating ionic liquid-gold nanoparticle systems that improve drug delivery to the brain.

## Contribution

The study introduces a rational design approach for integrating ionic liquids with gold nanoparticles for enhanced therapeutic delivery.

## Key findings

- IgG-IL-AuNPs showed 7.6-fold increased delivery across the blood–brain barrier in vivo.
- The formulations exhibited enhanced structural, thermal, and thermodynamic stability.
- Supramolecular assemblies were fine-tuned through IL cation and anion selection.

## Abstract

Ionic liquid (IL) nanotechnology holds significant promise
for
designing nanoscale materials with tunable viscosity, polarity, and
thermal stability for advanced therapeutic applications. However,
the field currently lacks comprehensive guidelines for integrating
ILs into complex therapeutic formulations. Herein, we propose the
key design considerations for engineering immunoglobulin G (IgG) conjugated
to gold nanoparticles (AuNPs) in the presence of choline-based ILs.
By judicious IL cation and anion selection, we fine-tune the supramolecular
assemblies and leverage the unique physicochemical properties of ILs
to impart AuNPs with advantageous characteristics including enhanced
structural, thermal, and thermodynamic stabilities, highly tunable
morphologies, and markedly reduced aggregation propensities. Through
systematic circular dichroism measurements, the thermodynamic parameters
of the complex formulations were determined, offering insight into
the IgG conformational changes and design parameters for systems of
enhanced IgG conjugation to AuNP surfaces. In demonstrating the power
of our design approach, the complex formulation of IgG-choline chloride-AuNPs,
also including trehalose, histidine, and arginine, was delivered via
focused ultrasound and microbubbles across the blood–brain
barrier and showed a 7.6-fold increase in delivery in vivo compared to the traditional formulation. We demonstrate that IgG-IL-AuNPs
can be easily and precisely manipulated at the nanometer scale, enabling
the formation of versatile structural configurations. Holistically,
we believe the rational design approach developed will advance the
engineering of tailored IL-nanocarriers for targeted therapeutic delivery
and broaden the scope of IL applications in biomedicine.