From Dyestuff Chemistry to Cancer Theranostics: The Rise of Rylenecarboximides

Abstract

CONSPECTUS: Fighting cancer with the means of chemistry remains a tremendous challenge and defines a pressing societal need. Compounds based on synthetic organic dyes have long been recognized as vital tools for cancer diagnosis and therapy (theranostics). Fluorescence and photoacoustic imaging of cancer as well as cancer treatment protocols such as photodynamic and photothermal therapy are all photobased technologies that require chromophores. However, a serious drawback of most chromophoric molecules is photobleaching over the course of their use in biological environments, which severely compromises the desired theranostic effects. At this point, rylenecarboximide (RI) dyes with ultrahigh photostability hold enormous promise. RI stands for a homologous series of dyes consisting of an aromatic core and carboximide auxochromic groups. They possess high molar extinction coefficients and finely tunable photophysical properties. RIs such as perylenebiscarboxylic acid monoimide (PMI), perylenetetracarboxylic acid diimide (PDI), terrylenetetracarboxylic acid diimide (TDI), and quaterrylene tetracarboxylic acid diimide (QDI) have attracted great scientific attention as colorants, components of organic photovoltaics and organic field-effect transistors, as well as tools for biological applications. PDI has appeared as one of the most widely studied RI dyes for fluorescence bioimaging. Our recent breakthroughs including chemotherapy with PDI-based DNA intercalators and photothermal therapy guided by photoacoustic imaging using PDI, TDI, or QDI, define urgent needs for further scientific research and clinical translation. In this Account, we tackle the relationship between chemical structures and photophysical and pharmacologic properties of RIs aiming at new contrast and anticancer agents, which then lay the ground for further biomedical applications. First, we introduce the design concepts for RIs with a focus on their structure−property relationships. Chemical structure has an enormous impact on the fluorescent, chemotoxic, photodynamic, and photothermal performance of RIs. Next, based on the resulting performance criteria, we employ RIs for fluorescence and photoacoustic cancer imaging as well as cancer therapies. When carrying electron donating substituents, PDIs and PMIs possess high fluorescence quantum yield and red-shifted emission which qualifies them for use in cancer fluorescence imaging. Also, some fluorescent PDIs are combined with chemodrugs or developed into DNA intercalators for chemotherapy. PDI-based photosensitizers are prepared by "heavy atom" substitution, showing potential for photodynamic therapy. Further, photothermal agents using PDI, TDI, and QDI with near-infrared absorption and excellent photothermal conversion efficiency offer high promise in photothermal cancer therapy monitored by photoacoustic imaging. Finally, looking jointly at the outstanding properties of RIs and the demands of current biomedicine, we offer an outlook toward further modifications of RIs as a powerful and practical pla...

Tuning the stability of organic radicals: from covalent approaches to non-covalent approaches

“…Besides the encapsulation of organic radicals as guest molecules, the fabrication of ordered supramolecular structures based on organic radials can also provide steric protection to the radicals. Yin et al reported the use of a perylenediimide (PDI) derivative and Zr-cluster to fabricate a metal-organic framework Zr-PDI 55,56 (Fig. 9).…”

Perylene Diimide-Based Fluorescent and Colorimetric Sensors for Environmental Detection

“…In addition to the great extensibility for development as diverse modes of chemosensors targeting broad range of environment analytes, PDI-based materials also possess other unique features, such as remarkably strong thermal/chemical/photochemical stability, environment benignity, good biocompatibility, and low cytotoxicity [3,37,[62][63][64]. Indeed, due to these superior features (compared to most of other chemosensors), PDI-based fluorescence and colorimetric sensors, as well as the related molecular probes, have already been extensively employed in physiological and food detections [62], cell imaging and related biological probing [22,30,33,35,37,40], and biomedical imaging and photodynamic therapy [63,64]. Moreover, the great success of PDI-based sensors in liquid-phase detection can be extended onto development of solid-phase sensors, e.g., thin films, which will further mitigate the risk of toxicity impact to the environment.…”

Functional organic dyes for health‐related applications

“…82 Several rylenecarboximides (PDI, TDI, and QDI) based photothermal agents have been developed for photoacoustic imaging-guided PTT. [83][84][85][86] Through π-conjugation extension or construction of D-π-A structures, dyes with higher photothermal conversion efficiencies (up to 64%) can be obtained ( Figure 8A). 86 Especially, TDI and QDI based photothermal agents can self-assemble into ultrasmall nanoparticles (∼10 nm), favoring for deep penetration of tumor tissues and achieved high resolution tumor photoacoustic images.…”