Perylene-diimide-based nanoparticles as highly efficient photoacoustic agents for deep brain tumor imaging in living mice

Abstract

In order to promote preclinical and clinical applications of photoacoustic imaging, novel photoacoustic contrast agents are highly desired for molecular imaging of diseases, especially for deep tumor imaging. Here, perylene-3,4,9,10-tetracarboxylic diiimide-based near-infrared-absorptive organic nanoparticles are reported as an efficient agent for photoacoustic imaging of deep brain tumors in living mice with enhanced permeability and retention effect.

Keywords: Perylene-3,4,9,10-tetracarboxylic diimide nanoparticles; brain tumor; deep tumor imaging; near-infrared-absorption; photoacoustic imaging.

Figure 1

a) Schematically illustrating the PAI process of brain tumor in vivo by PDI NPs. b) Picture of PDI NPs in PBS (pH = 7.4). c) TEM of PDI NPs (Bar = 100 nm). d) Hydrodynamic size distribution graph of PDI NPs. e) UV–vis–NIR absorption spectrum of PDI NPs in aqueous solution. f) Photostability comparison of PDI NPs with ICG.

Figure 2

a) The US (grey), PA (green), and their overlay coronal sections of brain of control model (top) and tumor model (bottom) before and after tail vein injection of 250 μL of 250 nM PDI NPs. b) The relative PA signal changes of the skull region (S, in red dotted circle of (a)) and tumor region (T, in blue dotted circle of (a)) at 2 d compared with that at 1 d, respectively, and that of T/S at 1 d and 2 d. c) PA spectra of PDI NPs in aqueous solution (black line), the region in red dotted circle of (a) before injection of NPs (red line) and tumor region of (a) after 2 d injection of NPs (blue line). d) The PA coronal sections of PDI NPs with different concentrations (from 50 to 0.390625 nM) in agarose gel (in vivo phantom). e) The plots of PA intensity–NP concentration and PA detectable depth–NP concentation relationships.

Figure 3

a) The ultrasonic (grey), photoacoustic (green), and their overlay coronal sections of brain of control model (left) and tumor model (right) which were harvested and buried in agarose gel after 2 d tail vein injection of PDI NPs. b) Photographic transverse imaging (left) and the overlay of PA (green) and US (grey) sagittal 3D image (right) of tumor bearing brain. The red dot in fi gure (b) is the injection point of C6-Fluc cell.