外渗
脂质体
荧光
荧光显微镜
荧光寿命成像显微镜
共焦显微镜
体内
磷脂
生物物理学
共焦
病理
活体显微镜检查
纳米载体
化学
显微镜
癌症研究
医学
生物
细胞生物学
生物化学
药理学
几何学
药品
生物技术
物理
量子力学
膜
数学
作者
Guankui Wang,Μαρκέλλα Ζαννίκου,Laren A. Lofchy,Yue Li,Hanmant Gaikwad,Irina V. Balyasnikova,Dmitri Simberg
出处
期刊:ACS Nano
[American Chemical Society]
日期:2021-07-01
卷期号:15 (7): 11880-11890
被引量:16
标识
DOI:10.1021/acsnano.1c02982
摘要
Tumor trafficking of liposomes is routinely monitored via fluorescence microscopy and imaging. To investigate whether an accumulation of liposomes depends on the type of fluorescent label, we prepared PEGylated liposomes dual-labeled with indocarbocyanine lipids (ICLs: DiD or DiI) and fluorescent phospholipids (FPLs: Cy3-DSPE or Cy5-DSPE) with similar cyanine headgroups but different spectra. Using ex vivo confocal microscopy and imaging, we compared tumor extravasation and accumulation of ICLs and FPLs. After systemic injection in a syngeneic mouse model of 4T1 breast cancer, ICLs and FPLs initially colocalized in tumor blood vessels and perivascular space. At later time points, ICLs spread over a significantly larger tumor area and accumulated in tumor macrophages, whereas FPLs were mostly restricted to the vasculature with limited extravascular signal. This phenomenon was independent of liposomal composition and ICL/FPL type and was also observed in syngeneic intracranial GL261 glioma and LY2 head and neck cancer models. The dual-labeled liposomes were stable in plasma and delivered both dyes to tumors at early time points. Notably, while the level of ICLs increased over time, FPLs gradually disappeared from tumors and other organs in vivo, likely due to degradation of the phospholipid. These findings demonstrate that trafficking and stability of the label is of critical importance when assessing extravasation and accumulation of nanocarriers in tumors and other organs by fluorescence microscopy and imaging.
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