The early and accurate detection of myocarditis is of great significance for timely therapeutic intervention and effectively avoiding subsequent fatal cardiovascular events. However, the currently reported methods are not competent for this attempt. Benefit from the excellent properties of optical imaging and nanoscience, a high-performance nano-fluorescent probe was tactfully constructed in this work by taking full advantage of the specific biomarker in the acute myocarditis and an aggregation-induced emission-active molecule with second near-infrared (NIR-II) emission. A systematic study on signature immune cells and relevant targets in the acute phase of myocarditis in both mice and human samples demonstrated that the chemokine of CXCL9 is specifically overexpressed in the inflammatory macrophages. The corresponding anti-CXCL9 sequence peptide was custom-synthesized and modified to the periphery of nanoprobe. The efficient and specific targeting of myocarditis in the acute stage by the prepared CXCL9+ macrophages-targeted nanoprobes (TNPs) was confirmed by using the established experimental autoimmune myocarditis (EAM) mice. Moreover, the TNPs exhibited the ability to detect human myocarditis samples in vitro. Noteworthily, the drug treatment efficacy on myocarditis was also accurately evaluated through monitoring the NIR-II fluorescence intensity variation at myocarditis sites, providing a robust tool for anti-myocarditis drug screening. This study is the first investigation of nano-fluorescent probes for the acute phase of myocarditis diagnosis and showed great potential for clinical applications.

Photoimmunotherapy has been acknowledged to be an unprecedented strategy to obtain significantly improved cancer treatment efficacy. In this regard, the exploitation of high-performance multimodal phototheranostic agents is highly desired. Apart from tailoring electron donors, acceptor engineering is gradually rising as a deliberate approach in this field. Herein, we rationally designed a family of aggregation-induced emission (AIE)-active compounds with the same donors but different acceptors based on the acceptor engineering. Through finely adjusting the functional groups on electron acceptors, the electron affinity of electron acceptors and the conformation of the compounds were simultaneously modulated. It was found that one of the molecules (named DCTIC), bearing a moderately electrophilic electron acceptor and the best planarity, exhibited optimal phototheranostic properties in terms of light-harvesting ability, fluorescence emission, reactive oxygen species (ROS) production, and photothermal performance. For the purpose of amplified therapeutic outcomes, DCTIC was fabricated into tumor and mitochondria dual-targeted DCTIC nanoparticles (NPs), which afforded good performance in the fluorescence/photoacoustic/photothermal trimodal imaging-guided photodynamic/photothermal-synergized cancer immunotherapy with the combination of programmed cell death protein-1 (PD-1) antibody. Not only the primary tumors were totally eradicated, but efficient growth inhibition of distant tumors was also realized.

Three-photon fluorescence (3PF) imaging excited at 1700 nm window is an enabling technology for visualizing deep brain structures and dynamics. Recently, the 2200 nm window has emerged as the longest excitation window suitable for deep-brain 3PF imaging. Bright fluorescent probes lay the material basis for deep-brain 3PF imaging. Among various fluorescent probes, aggregation-induced emission luminogens (AIEgens) have great potential in 3PF imaging excited at the 1700 nm window in vivo. However, to the best of knowledge, there is no AIEgens applicable to 3PF imaging excited at both the 1700 and 2200 nm windows. To readily fill this gap, here this study designs and synthesizes a novel AIEgen, namely TPE-DPTT-ICP, which generates bright 3PF signals excited at both 1700 and 2200 nm. The accordingly fabricated TPE-DPTT-ICP nanoparticles (NPs) possess excellent water dispersibility, colloidal stability, biocompatibility, photostability and large 3P action cross section, key to in vivo imaging. In mouse brain in vivo, TPE-DPTT-ICP NPs enable deepbrain 3PF imaging of subcortical structures excited at both the two windows, reaching depths of 1640 and 880 mu m below the brain surface, respectively. TPE-DPTT-ICP NPs are thus a versatile material simultaneously catering to the need at two infrared optical windows with deep tissue penetration.

Development of type I photosensitizers (PSs) with strong hydroxyl radical (· OH) formation is particularly important in the anaerobic tumor treatment. On the other hand, it is challenging to obtain an efficient solid-state intramolecular motion to promote the development of molecular machine and molecular motor. However, the relationship between them is never revealed. In this work, a pyrazine-based near-infrared type I PS with remarkable donor-acceptor effect is developed. Notably, the intramolecular motions are almost maximized by the combination of intramolecular and intermolecular engineering to simultaneously introduce the unlimited bond stretching vibration and boost the group rotation. The photothermal conversion caused by the intramolecular motions is realized with efficiency as high as 86.8%. The D-A conformation of PS can also induce a very small singlet-triplet splitting of 0.07 eV, which is crucial to promote the intersystem crossing for the triplet sensitization. Interestingly, its photosensitization is closely related to the intramolecular motions, and a vigorous motion may give rise to a strong · OH generation. In view of its excellent photosensitization and photothermal behavior, the biocompatible PS exhibits a superior imaging-guided cancer synergistic therapy. This work stimulates the development of advanced PS for the biomedical application and solid-state intramolecular motions.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied. It was demonstrated that the 1A system presented a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon, along with the increased acceptor electrophilicity and planarity. In sharp contrast, the 2A system with one more acceptor exhibited an opposite ACQ-to-AIE transformation. Interestingly, the fluorophore with a more electron-deficient A-A moiety in the 2A system displayed superior AIE activity. More importantly, all compounds in the 2A system showed significantly higher molar absorptivity (ε) in comparison to their counterparts in the 1A system. Thanks to the highest ε, near-infrared-II (NIR-II, 1000-1700 nm) emission, desirable AIE property, favorable reactive oxygen species (ROS) generation, and high photothermal conversion efficiency, a representative member of the 2A system handily performed in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal collaborative therapy for efficient tumor elimination. Meanwhile, the NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice was also accomplished. This study provides the first evidence that the dual-connected acceptor tactic could be a new molecular design direction for the AIE effect, resulting in high ε, aggregation-intensified NIR-II fluorescence emission, and improved ROS and heat generation capacities of phototheranostic agents.

Integrating the ultralong excitation wavelength, high extinction coefficient, and prominent photothermal conversion ability into a single photothermal agent is an appealing yet significantly challenging task. Herein, a precise dual-acceptor engineering strategy is exploited for this attempt based on donor-acceptor (D-A) type semiconductor polymers by subtly regulating the molar proportions of the two employed electron acceptor moieties featuring different electronic affinity and π-conjugation degrees, and making full use of the active intramolecular motion-induced photothermal effect. The optimal polymer SP4 synchronously shows desirable second near-infrared (NIR-II) absorption, an extremely high extinction coefficient, and satisfactory photothermal conversion behavior. Consequently, the unprecedented performance of SP4 NPs on 1064 nm laser-excited photoacoustic imaging (PAI)-guided photothermal therapy (PTT) is demonstrated by the precise tumor diagnosis and complete tumor elimination.

Construction of versatile nanotemplate bearing inherent distinctive functions and prominent drug-carrying capability is an appealing yet significantly challenging task. Here, inspired by the guiding role of surfactant in preparing nanoparticles, an amphiphilic aggregation-induced emission (AIE) photosensitizer, namely MeOTTVP, is synthesized with attractive near-infrared (NIR) emission and high-performance reactive oxygen species production, and followed by dual-templating-assisted one-pot method involving MeOTTVP as the skeleton to fabricate organosilica nanoparticles (AIE-ONs). The presented AIE-ONs perfectly inherit the functions of MeOTTVP, and are also capable of loading antibiotics and anticancer drugs. Doxorubicin can be assembled on AIE-ONs and then capped with hyaluronic acid, endowing the resulting hybrid with NIR fluorescence imaging-guided synergetic photodynamic/chemotherapy performance, thereby offering boosted anticancer efficacy and reduced side effects. Furthermore, by loading antibiotic rifampicin, the newly obtained AIE-ONs integrating chemo-photodynamic antibacterial functions provide broad-spectrum antibacterial activity and fluorescence monitoring behavior. This study thus not only offers a promising strategy to fabricate NIR nanoparticles on a large scale, but also provides useful insights into designing an advanced theranostic protocol for treating both cancer and bacterial infections.

The ingenious manipulation of electron donor/acceptor (D/A) has long been the major trend for advanced optoelectronic materials. In this context, benefitting from the diversity of electron donor species, donor engineering studies have ob-tained vigorous explorations, whereas the research on acceptor engineering received a snub by contrast. By learning from the philosophical idea of “more is different”, two types of compounds with the molecular structures of D−D−A−D−D (abbreviated as 1A system) and D−D−A−A−D−D (abbreviated as 2A system) based on acceptor engineering were un-precedentedly designed and studied. It was demonstrated that the compounds in 1A system presented an alteration from weak aggregation-induced emission (AIE) tendency to aggregation-caused quenching (ACQ) phenomenon along with the enhancement of electron-withdrawing capacity of the acceptors. Interestingly, the 2A system exhibited an opposite change of ACQ-to-AIE transformation when more electron-deficient acceptors were employed, manifesting that the in-troduction of an extra acceptor could largely contribute to the AIE feature. Thanks to the second near-infrared (NIR-II) window emission, superior AIE effect, favorable reactive oxygen species production ability and excellent photothermal conversion efficiency, 2TT-2BBTD (a member of 2A system) nanoparticles were proved to be handily competent in fluo-rescence-photoacoustic-photothermal multimodal imaging-guided photodynamic and photothermal therapy for eliminat-ing the orthotopic 4T1 mouse breast carcinoma. This work provides a fascinating molecular design philosophy for devel-oping versatile phototheranostic agent with a higher molar absorptivity, superb aggregation-intensified NIR-II fluorescent emission, and improved heat generation capacity.

Developing effective intelligent nanotheranostics is highly desirable for cancer treatment but remains challenging. In this study, an acidic tumor microenvironment-activated organosilica nanosystem, namely AD-Cu-DOX-HA, is straightforwardly constructed, which is composed of aggregation-induced emission (AIE)-active photosensitizer, copper ion-engineered aminosilica, direct coordination polymer of doxorubicin (DOX), and targeting component hyaluronic acid (HA). AD-Cu-DOX-HA is able to accurately distinguish cancer cells over normal cells; meanwhile, it simultaneously exhibits selective accumulation and copper ion-mediated rapid disassembly and turn-on fluorescence in tumor tissue, consequently achieving efficient tumor diagnosis and tumor-growth inhibition through fluorescence imaging-navigated synergetic photodynamic therapy, copper ion-mediated chemodynamic therapy, and DOX-enabled chemotherapy. This work thus brings fresh insight into the exploration of versatile theranostics and presents a momentous advance for potential clinical cancer treatment.

The manipulation of electron donor/acceptor (D/A) shows endless impetus for innovating optoelectronic materials. Because of the diversity of electron-donating species, the study on donor engineering has explored systematically, whereas the research on electron acceptor engineering received a snub by contrast. Inspired by the philosophical idea of “more is different”, two systems with D'−D−A−D−D' (1A system) and D'−D−A−A−D−D' (2A system) structures based on the acceptor engineering are ingeniously designed and studied. It is demonstrated that the 1A system presents a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon along with the increased acceptor electrophilicity. Interestingly, the 2A system exhibits an opposite ACQ-to-AIE transformation, manifesting the dual-acceptor tactic could facilitate AIE activity. Thanks to the highest molar absorptivity, near-infrared-II (NIR-II, 1000–1700 nm) emission, superior AIE effect, favorable reactive oxygen species generation and high photothermal conversion efficiency, a representative member of 2A system handily perform in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal synergetic therapy for efficient tumor elimination. Meanwhile, NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice are also accomplished. This work provides a fascinating molecular design philosophy for developing versatile phototheranostic agent with a higher molar absorptivity, superb aggregation-intensified NIR-II fluorescent emission, and improved heat generation capacity.