A Diradicaloid Small Molecular Nanotheranostic with Strong Near-Infrared Absorbance for Effective Cancer Photoacoustic Imaging and Photothermal Therapy

Abstract

Organic small molecule-based phototheranostics hold great promise for clinical translation by virtue of their distinct chemical structure, easy reproducibility, and high purity. However, reported molecular agents typically have relatively low optical absorbances, particularly over the near-infrared (NIR) region, and this limits their phototheranostic performance. Herein, we first exploit a diradicaloid molecular structure for enhancing NIR absorption to facilitate efficient photoacoustic imaging (PAI)-guided photothermal therapy (PTT). The donor–acceptor interaction in the diradicaloid molecule (DRM) leads to strong charge transfer resulting on obvious diradical characteristics, which is beneficial for NIR absorption. The DRM possesses excellent light-harvesting ability, with a mass extinction coefficient of ∼220 L g–1 cm–1, which is much higher than those (∼5–100 L g–1 cm–1) of typical organic molecules. After assembling into nanoparticles, they show good water dispersibility, good photostability, and impressive performance for PAI-guided PTT in vitro and in vivo. The impressive in vitro and in vivo performances show that developing small molecules with diradicaloid structures can be an effective approach for enhancing NIR harvesting capability for biomedical applications.

Organic radical materials in biomedical applications: State of the art and perspectives

“…Reproduced with permission. [45] Copyright 2021, American Chemical Society from 16.3% to 31.6%. Compared with traditional radical synthesis method via covalent chemistry, the method they established via supramolecular chemistry is much simpler.…”

“…Lee et al also exploit a novel carbon-centered diradical DRM, which is composed of a strong donor (N,N-bis(4-butoxyphenyl)thiophen-2-amine) and a robust acceptor (croconic acid), as shown in Figure 8E. [45] Obvious feature of radical was observed in EPR spectra of the DRM because of efficient charge transfer via interaction between donor and acceptor (Figure 8F). After assembling DRM into nanoparticles (Figure 8E), DRM NPs show desirable absorption at∼790 nm, which is highly favorable for NIR PTT.…”

Conjugated Polymers: Optical Toolbox for Bioimaging and Cancer Therapy

“…Currently, more recent studies have shown superior performance of CPs in the PA imaging field and successfully applied for real-time photoactivable theranostics. [130][131][132][133][134] [104] Copyright 2017, Nature Publishing Group.…”

Molecular Programming of NIR‐IIb‐Emissive Semiconducting Small Molecules for In Vivo High‐Contrast Bioimaging Beyond 1500 nm

“…[37,39,40] Taking advantage of their tunable molecular structures, light-harvesting windows of semiconducting small molecules can easily covered the entire visible and the NIR regions, thus holding great promise for various biomedical applications. [38,[41][42][43][44][45][46][47][48][49][50][51] Notably, recent advances in semiconducting small molecules-based non-radiative transitions have been made for efficient photothermal therapy (PTT) and photoacoustic imaging (PAI) in vivo, especially in the NIR-I and the NIR-II windows. In respect of fluorescence properties, semiconducting small molecules can effectively coordinate the conjugated units to achieve high brightness fluorescence in the visible and the NIR ranges.…”