Fluorescence imaging in near-infrared IIb (NIR-IIb, 1500–1700 nm) spectrum holds a great promise for tissue imaging. While few inorganic NIR-IIb fluorescent probes have been reported, their organic counterparts are still rarely developed, possibly due to the shortage of efficient materials with long emission wavelength. Herein, we propose a molecular design philosophy to explore pure organic NIR-IIb fluorophores by manipulation of the effects of twisted intramolecular charge transfer and aggregation-induced emission at the molecular and morphological levels. An organic fluorescent dye emitting up to 1600 nm with a quantum yield of 11.5% in the NIR-II region is developed. NIR-IIb fluorescence imaging of blood vessels and deeply-located intestinal tract of live mice based on organic dyes is achieved with high clarity and enhanced signal-to-background ratio. We hope this study will inspire further development on the evolution of pure organic NIR-IIb dyes for bio-imaging. Light has limited penetration depth in vivo which has led to increasing interest in NIR-II fluorophores. Here, the authors report on the design and testing of an organic aggregation induced emission fluorophore with high quantum yield and demonstrate imaging of vasculature and intestines in live mice.

/pdf/design-of-aiegens-for-near-infrared-iib-imaging-through-31ccyphgna.pdf

Design of AIEgens for near-infrared IIb imaging through structural modulation at molecular and morphological levels.

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) using small-molecule dyes has high potential for clinical use. However, many NIR-II dyes suffer from the emission quenching effect and extremely low quantum yields (QYs) in the practical usage forms. The AIE strategy has been successfully utilized to develop NIR-II dyes with donor-acceptor (D-A) structures with acceptable QYs in the aggregate state, but there is still large room for QY improvement. Here, we rationally designed a NIR-II emissive dye named TPE-BBT and its derivative (TPEO-BBT) by changing the electron-donating triphenylamine unit to tetraphenylethylene (TPE). Their nanoparticles exhibited ultrahigh relative QYs of 31.5% and 23.9% in water, respectively. By using an integrating sphere, the absolute QY of TPE-BBT nanoparticles was measured to be 1.8% in water. Its crystals showed an absolute QY of 10.4%, which is the highest value among organic small molecules reported so far. The optimized D-A interaction and the higher rigidity of TPE-BBT in the aggregate state are believed to be the two key factors for its ultrahigh QY. Finally, we utilized TPE-BBT for NIR-II photoluminescence (PL) and chemiluminescence (CL) bioimaging through successive CL resonance energy transfer and Förster resonance energy transfer processes. The ultrahigh QY of TPE-BBT realized an excellent PL imaging quality in mouse blood vessels and an excellent CL imaging quality in the local arthrosis inflammation in mice with a high signal-to-background ratio of 130. Thus, the design strategy presented here brings new possibilities for the development of bright NIR-II dyes and NIR-II bioimaging technologies.

Rational Design of NIR-II AIEgens with Ultrahigh Quantum Yields for Photo- and Chemiluminescence Imaging.

The construction of supramolecular coordination complexes (SCCs) featuring prominent cancer theranostic functions is an appealing yet significantly challenging task. In this study, we rationally designed and facilely constructed a prism-like metallacage C-DTTP with efficient fluorescence emission in the second near-infrared (NIR-II) region through the assembly of an aggregation-induced emission-active four-arm ligand with 90° Pt acceptors Pt(PEt3)2(OTf)2. C-DTTP held the longest maximum emission wavelength (1005 nm) compared with those previously reported SCCs up to now and exhibited both a high photothermal conversion efficiency (39.3%) and significantly superior reactive oxygen species generation behavior to the precursor ligand. In vitro and in vivo assessments demonstrated that the metallacage-loaded nanoparticles with excellent biocompatibility and stability were capable of simultaneously affording precise tumor diagnosis and complete tumor elimination by means of NIR-II fluorescence/photothermal dual imaging-guided photodynamic/photothermal synergistic therapy.

Self-Assembled Metallacage with Second Near-Infrared Aggregation-Induced Emission for Enhanced Multimodal Theranostics.

Mitochondria-targeted smart AIEgens: Imaging and therapeutics

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice. 

/pdf/enhancing-the-therapeutic-efficacy-of-nanoparticles-for-16hldfnu.pdf

Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies

Photo-driven theranostics, also known as phototheranostics, relying on the diverse excited-state energy conversions of theranostic agents upon photoexcitation represents a significant branch of theranostics, which ingeniously integrate diagnostic imaging and therapeutic interventions into a single formulation. The combined merits of photoexcitation and theranostics endow photo-driven theranostics with numerous superior features. The applications of aggregation-induced emission luminogens (AIEgens), a particular category of fluorophores, in the field of photo-driven theranostics have been intensively studied by virtue of their versatile advantageous merits of favorable biocompatibility, tuneable photophysical properties, unique aggregation-enhanced theranostic (AET) features, ideal AET-favored on-site activation ability and ready construction of one-for-all multimodal theranostics. This review summarised the significant achievements of photo-driven theranostics based on AIEgens, which were detailedly elaborated and classified by their diverse theranostic modalities into three groups: fluorescence imaging-guided photodynamic therapy, photoacoustic imaging-guided photothermal therapy, and multi-modality theranostics. Particularly, the tremendous advantages and individual design strategies of AIEgens in pursuit of high-performance photosensitizing output, high photothermal conversion and multimodal function capability by adjusting the excited-state energy dissipation pathways are emphasized in each section. In addition to highlighting AIEgens as promising templates for modulating energy dissipation in the application of photo-driven theranostics, current challenges and opportunities in this field are also discussed.

The fast-growing field of photo-driven theranostics based on aggregation-induced emission.

Achieving stimulus-responsive ultralong room temperature phosphorescence (RTP) in organic materials especially with full-color tunable emissions is attractive and important but rarely reported. Here, a strategy was reported to realize stimulus-responsive RTP effect with color-tunable emissions by using water as solvent in the preparation process without any organic solvent through covalent linkage of arylboronic acids with different π conjugations and polymer matrix of polyvinyl alcohol. The yielded polymer films exhibit outstanding RTP performance (2.43 s). Furthermore, an excitation-dependent RTP film was obtained, and the afterglow color changes from blue to green, then to red as the excitation wavelength increases. The RTP property of all the above materials is sensitive to water and heat stimuli, because the rigidity of the system could be broken by water. Last, they were successfully applied in a multilevel information encryption and multicolor paper and ink.

https://www.science.org/doi/pdf/10.1126/sciadv.abl8392?download=true

Stimulus-responsive room temperature phosphorescence materials with full-color tunability from pure organic amorphous polymers

Tumor hypoxia seriously impairs the therapeutic outcomes of type II photodynamic therapy (PDT), which is highly dependent upon tissue oxygen concentration. Herein, a facile strategy of acceptor planarization and donor rotation is proposed to design type I photosensitizers (PSs) and photothermal reagents. Acceptor planarization can not only enforce intramolecular charge transfer to redshift NIR absorption but also transfer the type of PSs from type II to type I photochemical pathways. Donor rotation optimizes photothermal conversion efficiency (PCE). Accordingly, three 3,6-divinyl-substituted diketopyrrolopyrrole (DPP) derivatives, 2TPAVDPP, TPATPEVDPP, and 2TPEVDPP, with different number of rotors were prepared. Experimental results showed that three compounds were excellent type I PSs, and the corresponding 2TPEVDPP nanoparticles (NPs) with the most rotors possessed the highest PCE. The photophysical properties of 2TPEVDPP NPs are particularly suitable for in vivo NIR fluorescence imaging-guided synergistic PDT/PTT therapy. The proposed strategy is helpful for exploiting type I phototherapeutic reagents with high efficacy for synergistic PDT and PTT.

Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT.

Microbial infectious diseases, especially those caused by new and antibiotic-resistant pathogenic microbes, have become a significant threat to global human health. As an antibiotic-free therapy, phototherapy is a promising approach to treat microbial infections due to its spatiotemporal selectivity, non-invasiveness, minimal side effects, and broad antimicrobial spectrum. Although organic photosensitizer-based antimicrobial phototherapy has been extensively studied over the last decade, there has been no specific review article on this topic yet. It is important and timely to summarize recent research progress in this field. This tutorial review highlights the concept and significance of phototherapy and summarizes innovative types of organic photosensitizers with design strategies to deal with microbial infections. In addition, examples of organic antimicrobial photosensitizers, including antibacterial photosensitizers, antiviral photosensitizers, and antifungal photosensitizers are discussed. Finally, current challenges and future directions of organic photosensitizer-based phototherapy for clinical antimicrobial applications are presented. We believe that this tutorial review will provide general guidance for the future development of efficient photosensitizers and encourage preclinical and clinical studies for phototherapy-mediated antimicrobial treatments.

Organic photosensitizers for antimicrobial phototherapy.

Nonradiative decay invariably competes with radiative decay during the deexcitation process of matter. In the community of luminescence research, nonradiative decay has been deemed less attractive than radiative decay. However, all things in their being are good for something and so is nonradiative decay. As the molecular motion-facilitated nonradiative decay (MMFND) effect is inevitable in photophysical processes, it provides a new avenue to convert the harvested light energy into exploitable forms by harnessing the molecular motion. In many cases, active molecular motion enables thermal deactivation from excited states. In this review, recent advances in photothermal and photoacoustic systems with the MMFND character are summarized. We believe that the present rational engineering of molecular motion for efficient photothermal generation will deepen the understanding of the relationship between molecular motion and nonradiative decay and navigate people to rethink the positive aspects of nonradiative decay for the establishment of new light-controllable techniques.

B. Tang

Papers

The fast-growing field of photo-driven theranostics based on aggregation-induced emission.

Stimulus-responsive room temperature phosphorescence materials with full-color tunability from pure organic amorphous polymers

Acceptor Planarization and Donor Rotation: A Facile Strategy for Realizing Synergistic Cancer Phototherapy via Type I PDT and PTT.

Organic photosensitizers for antimicrobial phototherapy.

Molecular Motion and Nonradiative Decay: Towards Efficient Photothermal and Photoacoustic Systems.