Indocyanine Green J Aggregates in Polymersomes for Near-Infrared Photoacoustic Imaging

Abstract

Clinical translation of photoacoustic imaging (PAI) has been limited by the lack of near-infrared (NIR) contrast agents with low toxicity required for regulatory approval. Herein, J aggregates of indocyanine green (ICG) with strong NIR absorbance were encapsulated at high loadings within small 77 nm polymersomes (nanocapsules) composed of poly­(lactide-co-glycolide-b-poly­(ethylene glycol)) (PLGA-b-PEG) bilayers, thus enabling PAI of of breast and ovarian cancer cells with high specificity and a sensitivity at the level of ∼100 total cells. All of the major components of the polymersomes are FDA approved and used in the clinic. During formation of polymersomes with a water-in-oil-in-water double emulsion process, loss of ICG from the ICG J aggregates was minimized by coating them with a layer of branched polyethylenimine and by providing excess “sacrificial” ICG to adsorb at the oil–water interfaces. The encapsulated J aggregates were protected against dissociation by the polymersome shell for 24 h in 100% fetal bovine serum, after which the polymersomes biodegraded and the J aggregates dissociated to ICG monomers.

Assembly Induced Super-Large Red-Shifted Absorption: The Burgeoning Field of Organic Near-Infrared Materials

“…After coassembly with polymers like 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG 2000 -NH 2 ) or poly(lactide-co-glycolide-b-poly(ethylene glycol)) (PLGA-b-PEG), the ICG nanoparticles showed a significantly red-shifted peak at 895 nm. 35,36 In a similar manner, coassembly of an aza-BODIPY compound and amphiphilic DSPE-PEG 2000 under ultrasonic power afforded cubic nanoparticles showing two newly appearing absorption peaks at 721 and 772 nm, while the aza-BODIPY monomer and its H-aggregates showed absorptions at 658 and 624 nm, respectively. 37 Coassembly of an amphiphilic polymer H-PEG-PPG-PEG-OH and zinc phthalocyanine lead to a J-aggregate with the absorption peak red-shifting from 680 to ca.…”

Exploiting cyanine dye J-aggregates/monomer equilibrium in hydrophobic protein pockets for efficient multi-step phototherapy: an innovative concept for smart nanotheranostics

“…Unfortunately, these promising assemblies fail in in vivo applications as they are not thermodynamically stable in serum and dissociate within minutes. 28 Under this scenario, we hypothesized that J-ICG could be confined in a hydrophobic environment and prevent their uncontrolled dissociation. Moreover, the J-aggregate/monomer equilibrium could be exploited to improve the ICG performance in light to heat transduction derived from its poor photostability.…”

Synthesis of sialic acid conjugates of the clinical near-infrared dye as next-generation theranostics for cancer phototherapy

“…It is worth noting that after one day, the maximum absorption and peak shape of the UV spectrum of ICG in PBS changed with the observation of a narrow red-shifted absorbance peak at 870 nm, which is due to the formation of ICG aggregates. 38 In contrast, when stored in PBS for one day, negligible changes in the UV spectra of Sia-C2-ICG and Sia-C9-ICG were observed, indicating that no Sia-ICG aggregates were produced. After five days, the absorbance of ICG at 790 nm decreased by 81.4%, while the absorbance of Sia-C2-ICG and Sia-C9-ICG at 790 nm decreased by 0.5% and 3.5%, respectively.…”