Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells

Abstract

An elusive goal for systemic drug delivery is to provide both spatial and temporal control of drug release. Liposomes have been evaluated as drug delivery vehicles for decades, but their clinical significance has been limited by slow release or poor availability of the encapsulated drug. Here we show that near-complete liposome release can be initiated within seconds by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Our findings reveal that different coupling methods such as having the HGNs tethered to, encapsulated within, or suspended freely outside the liposomes, all triggered liposome release but with different levels of efficiency. For the underlying content release mechanism, our experiments suggest that the microbubble formation and collapse due to the rapid temperature increase of the HGN is responsible for liposome disruption, as evidenced by the formation of solid gold particles after the NIR irradiation and the coincidence of a laser power threshold for both triggered release and pressure fluctuations in the solution associated with cavitation. These effects are similar to those induced by ultrasound and our approach is conceptually analogous to the use of optically triggered nano-"sonicators" deep inside the body for drug delivery. We expect HGNs can be coupled with any nanocarriers to promote spatially and temporally controlled drug release. In addition, the capability of external HGNs to permeabilize lipid membranes can facilitate the cellular uptake of macromolecules including proteins and DNA and allow for promising applications in gene therapy.

Figure 1. Characterization of HGN/liposome complexes

(a-c) Cryo-EM images showing HGNs (red arrows) (a) encapsulated inside, (b) tethered to, and (c) suspended freely outside liposomes (blue arrows) ,. (d) Absorption spectrum of HGNs.

Figure 2. Effect of pulsed-laser power

(a) Kinetics of in situ fluorescence shows the rate of liposomal release induced by encapsulated HGNs at various laser powers. The solid lines are single exponential fits, F = Fo + Ae^−/τto the data. (b) Liposomal release as a function of laser power induced by HGNs encapsulated inside and suspended freely outside after 9 minutes irradiation. The solid curves are sigmoidal fit to the data: y = (y_max−y_min)/(1 + e^(E–Eo)/ΔE)+y_min The maximum release is different for the two coupling methods, but the threshold power for release is the same (2.2 W/cm²). (c) Typical photoacoustic signal of pressure fluctuations associated with cavitation recorded by a hydrophone from a 0.142 mM HGN solution after a single laser pulse (average power 16.1 W/cm²). The inset is an enlarged view. (d) Acoustic signal amplitude as a function of pulsed-laser power. A threshold of laser power at 2.3 W/cm² to induce the cavitation is similar to the threshold to trigger the liposomal contents release (Fig. 2b).

Figure 3. Morphology of HGN/liposome complex after laser irradiation

Cryo-EM images showing that HGNs become solid-core nanoparticle (red arrows) after NIR pulsed-laser irradiation (16.1 W/cm²), both inside (left) and outside (right) of the liposomes (blue arrows).