Photostable Iridium(III)–Cyanine Complex Nanoparticles for Photoacoustic Imaging Guided Near-Infrared Photodynamic Therapy in Vivo

Abstract

The iridium­(III)–cyanine complex (IrCy) was fabricated by conjugating an iridium­(III) complex to a cyanine dye with an intense near-infrared (NIR) absorption. IrCy complex nanoparticles (NPs) with high water solubility and photostability were prepared by a solvent evaporation-induced self-assembly strategy. Considering their effective photacoustic (PA) imaging and generation of 1O2 property with 808 nm laser irradiation in aqueous solution, PA imaging guided NIR-driven photodynamic therapy in vivo was effectively conducted in the 4T1 xenograft model. We developed a real-time PA imaging methodology to investigate the pharmacokinetics, tumor targeting, and biodistribution of IrCy NPs. Taking advantage of the analysis of the PA signal of the common iliac vein, the blood circulation half-life of IrCy NPs in mice was calculated to be ∼18 h, and the enhanced permeability and retention effect of IrCy NPs offered the maximum targeting property in the tumor at about 24 h. The obvious change of PA imaging signal in kidney and bladder confirmed IrCy NPs should be excreted partially from the urine system, and the PA signal decreased from 12.5× to 2.8× in the liver, and from 28.8× to 9.4× in the spleen also confirmed the hepatic metabolic pathway.

Polymethine dyes for PDT: recent advances and perspectives to drive future applications

“…Despite the demonstrated photoactivity of the cyanine to treat and reduce tumors [61,62,105,106], a single phototherapy approach seems to limit the in vivo therapeutic efficacy, particularly to treat extended and deep tumors [76,[107][108][109]. To overcome these drawbacks, a promising strategy could be the combination of different phototherapeutic approaches such as photodynamic and photothermal therapies.…”

Photosensitizer Anchored Nanoparticles: A Potential Material for Photodynamic Therapy

“…A solvent evaporation‐induced self‐assembly approach made Iridium Cyanine (IrCy) complex NPs with good water solubility and photostability [92] . TEM results showed that the size of the micellar structure reduced from 76 to 34 nm as the PEG length was increased.…”

Monitoring Immunotherapy With Optical Molecular Imaging

“…[40] Photoacoustic (PA) imaging combined with NIR excitation with thermal-ultrasonic detection can provide deeper tissue penetration, compared with fluorescence imaging. [41] The activatable PA imaging probes with biomarker-triggered signals can be used for in vivo imaging of biological biomarkers and metabolites at the molecular level, which is of great significance for real-time in vivo monitoring of immune response. [42] Zhang et al [35] developed a semiconducting polymer nanoprobe (SPNP) that detected the granzyme B released after CTLs immune activation by changing the near-infrared fluorescence (NIRF) and PA signal.…”

“…Due to high photon absorption and scattering, it is difficult for fluorescent probes to penetrate deeper tissues [40] . Photoacoustic (PA) imaging combined with NIR excitation with thermal‐ultrasonic detection can provide deeper tissue penetration, compared with fluorescence imaging [41] . The activatable PA imaging probes with biomarker‐triggered signals can be used for in vivo imaging of biological biomarkers and metabolites at the molecular level, which is of great significance for real‐time in vivo monitoring of immune response [42] .…”