Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release

Light-triggered drug
delivery systems enable site-specific and
time-controlled drug release. In previous work, we have achieved this
with liposomes containing gold nanoparticles in the aqueous core.
Gold nanoparticles absorb near-infrared light and release the energy
as heat that increases the permeability of the liposomal bilayer,
thus releasing the contents of the liposome. In this work, we replaced
the gold nanoparticles with the clinically approved imaging agent
indocyanine green (ICG). The ICG liposomes were stable at storage
conditions (4–22 °C) and at body temperature, and fast
near-infrared (IR) light-triggered drug release was achieved with
optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio.
Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa)
were completely released from the liposomes after light exposure for
15 s. Location of ICG in the PEG layer of the liposomes was simulated
with molecular dynamics. ICG has important benefits as a light-triggering
agent in liposomes: fast content release, improved stability, improved
possibility of liposomal size control, regulatory approval to use
in humans, and the possibility of imaging the in vivo location of
the liposomes based on the fluorescence of ICG. Near-infrared light
used as a triggering mechanism has good tissue penetration and safety.
Thus, ICG liposomes are an attractive option for light-controlled
and efficient delivery of small and large drug molecules.

光触发药物递送系统可实现位点特异性与时间可控的药物释放。既往研究中，我们通过制备水相核心负载金纳米颗粒的脂质体，实现了上述目标。金纳米颗粒可吸收近红外光，并以热量形式释放能量，提升脂质双分子层的通透性，进而释放脂质体所载的内容物。本研究中，我们将金纳米颗粒替换为临床获批的成像剂吲哚菁绿（indocyanine green, ICG）。该ICG脂质体在4~22℃的储存条件及体温下均保持稳定；通过优化磷脂组成并设置1:50的ICG与脂质摩尔比，可实现快速近红外（IR）光触发的药物释放。经15秒光照后，封装的小分子钙黄绿素与分子量最高达20 kDa的异硫氰酸荧光素-葡聚糖（FITC-dextran）可从脂质体中完全释放。我们通过分子动力学模拟，明确了ICG在脂质体聚乙二醇（PEG）层中的定位。作为脂质体中的光触发剂，ICG具备多项显著优势：可实现内容物快速释放、提升脂质体稳定性、优化脂质体粒径调控空间、获得人体使用的监管批准，还可通过ICG的荧光信号实现脂质体的体内定位成像。作为触发源的近红外光具备优异的组织穿透性与安全性。因此，ICG脂质体是实现小分子与大分子药物光控高效递送的极具潜力的候选方案。