Aiming to achieve versatile phototheranostics with the integrated functionalities of multiple diagnostic imaging and synergistic therapy, the optimum use of dissipated energy through both radiative and nonradiative pathways is definitely appealing, yet a significantly challenging task. To the best of the knowledge, there have been no previous reports on a single molecular species effective at affording all phototheranostic modalities including fluorescence imaging (FLI), photoacoustic imaging (PAI), photothermal imaging (PTI), photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, a simple and highly powerful one-for-all phototheranostics based on aggregation-induced emission (AIE)-active fluorophores is tactfully designed and constructed. Thanks to its strong electron donor-acceptor interaction and finely modulated intramolecular motion, the AIE fluorophore-based nanoparticles simultaneously exhibit bright near-infrared II (NIR-II) fluorescence emission, efficient reactive oxygen species generation, and high photothermal conversion efficiency upon NIR irradiation, indicating the actualization of a balance between radiative and nonradiative energy dissipations. Furthermore, the unprecedented performance on NIR-II FLI-PAI-PTI trimodal-imaging-guided PDT-PTT synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor elimination outcomes. This study thus brings a new insight into the development of superior versatile phototheranostics for practical cancer theranostics.

An All-Round Athlete on the Track of Phototheranostics: Subtly Regulating the Balance between Radiative and Nonradiative Decays for Multimodal Imaging-Guided Synergistic Therapy

Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due to the hypoxic nature characteristic of many solid tumors, PDT is frequently limited in therapeutic effect. Moreover, the consumption of O2 during PDT may further aggravate the tumor hypoxic condition, which promotes tumor proliferation, metastasis, and invasion resulting in poor prognosis of treatment. Therefore, numerous efforts have been made to increase the O2 content in tumor with the goal of enhancing PDT efficacy. Herein, these strategies developed in past decade are comprehensively reviewed to alleviate tumor hypoxia, including 1) delivering exogenous O2 to tumor directly, 2) generating O2 in situ, 3) reducing tumor cellular O2 consumption by inhibiting respiration, 4) regulating the TME, (e.g., normalizing tumor vasculature or disrupting tumor extracellular matrix), and 5) inhibiting the hypoxia-inducible factor 1 (HIF-1) signaling pathway to relieve tumor hypoxia. Additionally, the O2 -independent Type-I PDT is also discussed as an alternative strategy. By reviewing recent progress, it is hoped that this review will provide innovative perspectives in new nanomaterials designed to combat hypoxia and avoid the associated limitation of PDT.

Conquering the Hypoxia Limitation for Photodynamic Therapy

Photodynamic therapy (PDT) has shown great potential for tumor treatment with merits of non-invasiveness, high selectivity, and minimal side effects. However, conventional type II PDT relying on 1 O2 presents poor therapeutic efficacy for hypoxic tumors due to the oxygen-dependent manner. Alternatively, emerging researches have demonstrated that type I PDT exhibits superiority over type II PDT in tumor treatment owing to its diminished oxygen-dependence. In this review, state-of-the-art studies concerning recent progress in type I photosensitizers are scrutinized, emphasizing the strategies to construct highly effective type I photosensitizers. As the foundation, basic principles of type I PDT are presented, and up-to-date type I photosensitizers are summarized and classified based on their attributes. Then, a literature review of representative type I photosensitizers (including nanomaterials and small molecules) is presented with impetus to delineate their novel designs, action mechanisms, as well as anticancer PDT applications. Finally, the remaining challenges and development directions of type I photosensitizers are outlined, highlighting key scientific issues toward clinical translations.

Type I Photosensitizers Revitalizing Photodynamic Oncotherapy

Recent developments of BODIPY-based colorimetric and fluorescent probes for the detection of reactive oxygen/nitrogen species and cancer diagnosis

ROS-responsive cyclodextrin nanoplatform for combined photodynamic therapy and chemotherapy of cancer

Cancer phototheranostics, composed of optical diagnosis and phototherapy (including photodynamic therapy and photothermal therapy), is a promising strategy for precise tumor treatment. Due to the unique properties of near-infrared absorption/emission, high reactive oxygen species generation, and photothermal conversion efficiency, aza-boron-dipyrromethene (aza-BODIPY), as an emerging organic photosensitizer, has shown great potential for tumor phototheranostics. By encapsulating aza-BODIPY photosensitizers within functional amphiphilic polymers, we can afford hydrophilic nanomedicines that selectively target tumor sites via an enhanced permeability and retention effect, thereby efficiently improving diagnosis and therapeutic efficacy. Herein, in this spotlight article, we attempt to highlight our recent contributions in the development of aza-BODIPY-based nanomedicines, which comprises three main sections: (1) to elucidate the design strategy of aza-BODIPY photosensitizers and corresponding nanomedicines; (2) to overview their photophysical properties and biomedical applications in phototheranostics, including fluorescence imaging, photoacoustic imaging, photodynamic therapy, photothermal therapy, and synergistic therapy; and (3) to depict the challenges and future perspectives of aza-BODIPY nanomedicines. It is believed that this Spotlight on Applications article would illuminate the way of developing new aza-BODIPY nanomedicines as well as other organic photosensitizer-based nanomedicines for future clinical translation.

Aza-BODIPY-Based Nanomedicines in Cancer Phototheranostics.

Boosting O2•− Photogeneration via Promoting Intersystem-Crossing and Electron-Donating Efficiency of Aza-BODIPY-Based Nanoplatforms for Hypoxic-Tumor Photodynamic Therapy

Diketopyrrolopyrrole-derived organic small molecular dyes for tumor phototheranostics

Recent Progress of Acenaphthylene-imide-fused Polycyclic Aromatic Hydrocarbons: Synthesis and Application

N-type organic semiconductors are of great importance for organic electronics. Nevertheless, the development of n-type organic semiconductors is far lagged than its counterpart of p-type organic se...

Qianli Ma

Papers

Aza-BODIPY-Based Nanomedicines in Cancer Phototheranostics.

Boosting O2•− Photogeneration via Promoting Intersystem-Crossing and Electron-Donating Efficiency of Aza-BODIPY-Based Nanoplatforms for Hypoxic-Tumor Photodynamic Therapy

Diketopyrrolopyrrole-derived organic small molecular dyes for tumor phototheranostics

Recent Progress of Acenaphthylene-imide-fused Polycyclic Aromatic Hydrocarbons: Synthesis and Application

Linear acenaphthene-imide-fused pyrazinacene-quinone: synthesis and photophysical properties