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Liposomal J-Aggregates of Indocyanine Green (L-JA) can serve as a biocompatible and biodegradable nanoparticle for photoacoustic imaging and photothermal therapy. When compared to monomeric IcG, L-JA are characterized by longer circulation, improved photostability, elevated absorption at longer wavelengths, and increased photoacoustic signal generation. However, the documented methods for production of L-JA vary widely. We developed an approach to efficiently form IcG J-aggregates (IcG-JA) directly in liposomes at elevated temperatures. Aggregating within fully formed liposomes ensures particle uniformity and allows for control of J-aggregate size. L-JA have unique properties compared to IcG. L-JA provide significant contrast enhancement in photoacoustic images for up to 24 hours after injection, while IcG and unencapsulated IcG-JA are cleared within an hour. L-JA allow for more accurate photoacoustic-based sO2 estimation and particle tracking compared to IcG. Furthermore, photothermal heating of L-JA with an 852nm laser is demonstrated to be more effective at lower laser powers than conventional 808nm lasers for the first time. The presented technique offers an avenue for formulating a multi-faceted contrast agent for photoacoustic imaging and photothermal therapy that offers significant advantages over other conventional agents.

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A key challenge in the field of plexcitonic quantum devices is the fabrication of solid-state, device-friendly plexcitonic nanostructures using inexpensive and scalable techniques. Lithography-free, bottom-up nanofabrication methods have remained relatively unexplored within the context of plexcitonic coupling. In this work, a plexcitonic system consisting of thermally dewetted plasmonic gold nanoislands (AuNI) coated with a thin film of J-aggregates was investigated. Control over nanoisland size and morphology allowed for a range of plasmon resonances with variable detuning from the exciton. The extinction spectra of the hybrid AuNI/J-aggregate films display clear splitting into upper and lower hybrid resonances, while the dispersion curve shows anti-crossing behavior with an estimated Rabi splitting of 180 eV at zero detuning. As a proof of concept for quantum sensing, the AuNI/J-aggregate hybrid was demonstrated to behave as a plexcitonic sensor for hydrochloric acid vapor analyte. This work highlights the possibility of using thermally dewetted nanoparticles as a platform for high-quality, tunable, cost-effective, and scalable plexcitonic nanostructures for sensing devices and beyond.

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Here, it is shown that photoirradiation triggered chiral J-aggregates formation of an achiral anionic porphyrin, TPPS (tetrakis(4-sulfonatophenyl) porphyrin), in the presence of chiral triphenylamine (TPA) derivatives. A series of chiral triarylamines linked with aromatic rings is designed through urea or amide bonds. UV-irradiation of self-assembled urea-linked triphenylamine derivatives causes the formation of persistent radical cations in the chlorinated solvents, which subsequently induces the aggregation of TPPS. Transferring chirality of TPA derivatives to achiral TPPS J-aggregates leads to the chiral assemblies with remarkable chiroptical signals. The experimental results demonstrate that, TPA derivatives linked by the urea bond can effectively promote the aggregation of TPPS rather than those with the amide bond although the photo-generated radical cations are both produced. It is suggested that the urea-linked TPA derivatives are more favorable to stable radical cations and thus cause the formation of TPPS chiral J-aggregation. This work may open up an avenue for designing photo-modulated chiral supramolecular assemblies.

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Indocyanine green J-aggregates (ICG-Jagg) have emerged as a significant subject of interest in biomedical applications due to their unique optical properties, tunable size, and excellent biocompatibility. This comprehensive review aims to provide an in-depth exploration of ICG-Jagg, with a focus on elucidating the diverse facets of their preparation and the factors that influence the preparation process. Additionally, the review discusses their applications in biomedical diagnostics, such as imaging and contrast agents, as well as their utilization in drug delivery and various phototherapeutic interventions.

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Advanced photosensitizers for high-performance fluorescence imaging-guided photothermal therapy demand excellent near-infrared (NIR) brightness [molar absorption coefficient (ε) × quantum yield (QY)] and exceptional photothermal performance [ε × photothermal conversion efficiency (PCE)]. However, integrating high brightness and potent photothermal performance within a single molecule faces a formidable challenge. This article proposes a method to address this issue by preparing J-aggregate nanoparticles (NPs) using molecules with high ε. J-aggregates effectively improve QY and induce molecular emission redshift, while high ε molecules play a crucial role in improving the brightness and photothermal performance. By optimizing the molecular structure based on the pyrrolopyrrole cyanine (PPCy), precise control over the QY and PCE of PPCy J-aggregates is achieved. Ultimately, PDDO NPs exhibiting superior brightness (ε × QY = 3.32 × 104 M-1 cm-1) and photothermal performance (ε × PCE = 1.21 × 105 M-1 cm-1) are identified as high-performance photosensitizers. Notably, each parameter represents one of the highest levels among the reported fluorescence or photothermal probes to date. The in vivo studies demonstrate that PDDO NPs possess exceptional NIR imaging capabilities and remarkable photothermal tumor inhibition rates. This study provides innovative insights into the development of high-performance multifunctional photosensitizers.

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We introduce a two-step silica-encapsulation procedure to optimize both the optical efficiency and structural robustness of 5,5',6,6'-tetrachloro-1,1'-diethyl-3,3'-di(4-sulfobutyl)-benzimidazolocarbocyanine (TDBC), a two-dimensional sheet-like J-aggregate. We report a fluorescence quantum yield of ∼98%, the highest quantum yield recorded for any J-aggregate structure at room temperature, and a fast, emissive lifetime of 234 ps. Silica, as an encapsulating matrix, provides optical transparency, chemical inertness, and robustness to dilution, while rigidifying the J-aggregate structure. Our in situ encapsulation process preserves the excitonic structure in TDBC J-aggregates, maintaining their light absorption and emission properties. The homogeneous silica coating has an average thickness of 0.5-1 nm around J-aggregate sheets. Silica encapsulation permits extensive dilutions of J-aggregates without significant disintegration into monomers. The narrow absorbance and emission line widths exhibit further narrowing upon cooling to 79 K, which is consistent with J-type coupling in the encapsulated aggregates. This silica TDBC J-aggregate construct signifies (1) a bright, fast, and robust fluorophore system, (2) a platform for further manipulation of J-aggregates as building blocks for integration with other optical materials and structures, and (3) a system for fundamental studies of exciton delocalization, transport, and emission dynamics within a rigid matrix.

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Two star-shaped mesogens with a (meso-tetraphenylporphinato) zinc (II) core and bithiophene conjugated arms with 3,4,5-trisdodecyloxyphenyl periphery were synthesized. One of these molecules was decorated with four fullerenes via an aliphatic spacer. This is the sterically overcrowded compound with an octapodal morphology. The other star lacks the fullerenes and provides free space between the conjugated arms. This mesogen does not aggregate in solution, but in solid state it forms a hexagonal columnar and a highly ordered oblique helical columnar phase, while the octopus molecule assembles in an amorphous solid. Photophysical studies of the octapodal compound in solution and the solid thin film reveal the formation of J-type aggregates, in which the interaction between donors (porphyrin) and acceptors (fullerene) dominates leading to absorption bands in the NIR region of the spectra. The mixture of both compounds results in a self-assembly which is called the Click procedure. Fullerenes of the octopus nanosegregate in the pockets of the star mesogens generating hexagonal columnar structures with a regular stacking along the columnar axis. Thus providing free space is a tool to control the competition between supramolecular interactions and nanosegregation. Such liquid-crystalline donor-acceptor structures may play a role in future LC photovoltaic applications.

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The commonly employed strategies for engineering second near-infrared (NIR-II) organic phototheranostic agents are based on expanding conjugated backbone length, strengthening donor (D)-acceptor (A) effect, or forming J-aggregates. We constructed the D-A-D' structure by incorporating strong electron-donating methoxy and tetraphenylethene (TPE) moieties on the electron-deficient Aza-BODIPY core, and simultaneously expanded the π-conjugation effect by introducing thiophene groups, to obtain a dye BDP-TPE. Next, the nanoparticles P-TPE were prepared via the assembly of BDP-TPE with amphiphilic polypeptides (mPEG2000-P(Asp)10), and successfully constructed the J-aggregates. The obtained P-TPE exhibited strong absorption and fluorescence with maxima at 808 and 1018 nm, respectively, with a conspicuous absolute quantum yield of 0.241 %. Moreover, P-TPE also showed excellent biocompatibility, and high photothermal conversion efficiency of 61.15 %, and excellent resistance to pH, long-term storage, and photobleaching. In vitro and in vivo experiments revealed that P-TPE exhibited good biocompatibility and effectively achieved NIR-II fluorescence imaging-guided PTT with complete tumor ablation under 808 nm laser irradiation. These results provided good evidence for the use of P-TPE as a NIR-II fluorescence imaging-guided PTT therapeutic agent in vivo.

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Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.

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J-aggregation brings intriguing optical and electronic properties to molecular dyes and significantly expands their applicability across diverse domains, yet the challenge for rationally designing J-aggregating dyes persists. Herein, we developed a large number of J-aggregating dyes from scratch by progressively refining structure of a common heptamethine cyanine. J-aggregates with sharp spectral bands (full-width at half-maximum≤38 nm) are attained by introducing a branched structure featuring a benzyl and a trifluoroacetyl group at meso-position of dyes. Fine-tuning the benzyl group enables spectral regulation of J-aggregates. Analysis of single crystal data of nine dyes reveals a correlation between J-aggregation propensity and molecular arrangement within crystals. Some J-aggregates are successfully implemented in multiplexed optoacoustic and fluorescence imaging in animals. Notably, three-color multispectral optoacoustic tomography imaging with high spatiotemporal resolution is achieved, owing to the sharp and distinct absorption bands of the J-aggregates.

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The development of polymer-based persistent luminescence materials with color-tunable organic afterglow and multiple responses is highly desirable for applications in anti-counterfeiting, flexible displays, and data-storage. However, achieving efficient persistent luminescence from a single-phosphor system with multiple responses remains a challenging task. Herein, by doping 9H-pyrido[3,4-b]indole (PI2) into an amorphous polyacrylamide matrix, a hierarchical dual-mode emission system is developed, which exhibits color-tunable afterglow due to excitation-, temperature-, and humidity-dependence. Notably, the coexistence of the isolated state and J-aggregate state of the guest molecule not only provides an excitation-dependent afterglow color, but also leads to a hierarchical temperature-dependent afterglow color resulting from different thermally activated delayed fluorescence (TADF) and ultralong organic phosphorescence (UOP) behaviors of the isolated and aggregated states. The complex responsiveness based on the hierarchical dual-mode emission can serve for security features through inkjet printing and ink-writing. These findings may provide further insight into the regulated persistent luminescence by isolated and aggregated phosphors in doped polymer systems and expand the scope of stimuli-responsive organic afterglow materials for broader applications.

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Lithocholic acid (LCA), a secondary bile acid, has emerged as a potential early diagnostic biomarker for various liver diseases. In this study, we introduce a novel near-infrared (NIR) polymethine dye-based biosensor, capable of sensitive and selective detection of LCA in phosphate buffer and artificial urine (AU) solutions. The detection mechanism relies on the formation of J-aggregates resulting from the interplay of 3,3-Diethylthiatricarbocyanine iodide (DiSC2(7)) dye molecules and LCA, which induces a distinctive red shift in both absorption and fluorescence spectra. The biosensor demonstrates a detection limit for LCA of 70 µM in PBS solution (pH 7.4), while in AU solution, it responds to an LCA concentration as low as ∼60 µM. Notably, the proposed biosensor exhibits outstanding selectivity for LCA, effectively distinguishing it from common interferents such as uric acid, ascorbic acid, and glucose. This rapid, straightforward, and cost-effective spectrometer-based method underscores its potential for early diagnosis of liver diseases by monitoring LCA concentrations.

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NIR-IIa fluorescence imaging (FI) and NIR-II photothermal therapy (PTT) have gained popularity due to the advantages of high temporal and spatial resolution and deep penetration. However, the hyperthermia (>48 °C) of conventional PTT with nonspecific warming and thermal diffusion may inevitably cause damage to healthy tissues or organs surrounding the tumor. Therefore, it is highly desirable to provide effective cancer treatment by implementing mild photothermal therapy (mPTT) at mild temperatures with lower laser power density. Here, the nanotheranostic platform FN@P-GA NPs with NIR-II absorption and NIR-IIa emission was developed by constructing J-aggregates. FN@P-GA possesses good biocompatibility, favorable NIR-IIa FI performance, decent stability, and high photothermal conversion efficiency (57.6 %), which lays a solid foundation for FI-guided mPTT. Due to its ability to effectively down-regulate the expression of HSP90 and reduce cellular thermoresistance to kill cancer cells, FN@P-GA successfully achieved NIR-IIa FI-guided mPTT and demonstrated its potent anti-tumor effect under 1064 nm laser irradiation at mild temperature and low power density (0.3 W/cm2).

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The aggregation-induced emission (AIE) properties of a systematic series of naphthalene diimides (NDIs) varying the chain length at the imide positions have been studied. A solvophobic collapse of NDI units through the flash injection of THF NDI solutions in sonicating water triggers the formation of stable suspensions with enhanced fluorescence emissions. Shorter chains favor the π-π stacking of NDI units through H-aggregation producing a strong AIE effect showing remarkably high quantum yields that have not been observed for non core-substitued NDIs previously. On the other hand, NDIs functionalized with longer chains lead to more disordered domains where π-π stacking between NDI units is mainly given by J-aggregation unfavoring the AIE effect.

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Herein, the synthesis of two chiral NPBIs, (S)-1 and (R)-1, is reported and their self-assembling features investigated. The reported NPBIs form chiral supramolecular polymers with a rich dichroic pattern by the π-stacking of the aromatic backbones and the formation of an array of H-bonds between the amide functional groups. Furthermore, the peripheral 3,4,5-trialkoxy benzamide groups can form seven-membered pseudocycles by the intramolecular H-bonding interaction between the NH of the peripheral amides and one of the carbonyls of the imide units thus yielding a kinetically controlled self-assembly process. Unlike achiral NPBI 1, that has been reported to form up to four supramolecular polymorphs, the reported chiral NPBIs form only a J-type aggregated species. The results presented herein reveal how subtle changes exert an enormous influence on the supramolecular polymerization outcome.

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Achieving photothermal therapy (PTT) at ultralow laser power density is crucial for minimizing photo-damage and allowing for higher maximum permissible skin exposure. However, this requires photothermal agents to possess not just superior photothermal conversion efficiency (PCE), but also exceptional near-infrared (NIR) absorptivity. J-aggregates, exhibit a significant redshift and narrower absorption peak with a higher extinction coefficient. Nevertheless, achieving predictable J-aggregates through molecular design remains a challenge. In this study, we successfully induced desirable J-aggregation (λabs max : 968 nm, ϵ: 2.96×105  M-1 cm-1 , λem max : 972 nm, ΦFL : 6.2 %) by tuning electrostatic interactions between π-conjugated molecular planes through manipulating molecular surface electrostatic potential of aromatic ring-fused aza-BODIPY dyes. Notably, by controlling the preparation method for encapsulating dyes into F-127 polymer, we were able to selectively generate H-/J-aggregates, respectively. Furthermore, the J-aggregates exhibited two controllable morphologies: nanospheres and nanowires. Importantly, the shortwave-infrared J-aggregated nanoparticles with impressive PCE of 72.9 % effectively destroyed cancer cells and mice-tumors at an ultralow power density of 0.27 W cm-2 (915 nm). This phototherapeutic nano-platform, which generates predictable J-aggregation behavior, and can controllably form J-/H-aggregates and selectable J-aggregate morphology, is a valuable paradigm for developing photothermal agents for tumor-treatment at ultralow laser power density.

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Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.

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Molecular fluorophores emitting in the second near-infrared (NIR-II, 1000-1700 nm) window with strong optical harvesting and high quantum yields hold great potential for in vivo deep-tissue bioimaging and high-resolution biosensing. Recently, J-aggregates are harnessed to engineer long-wavelength NIR-II emitters and show unique superiority in tumor detection, vessel mapping, surgical navigation, and phototheranostics due to their bathochromic-shifted optical bands in the required slip-stacked arrangement aggregation state. However, despite the preliminary progress of NIR-II J-aggregates and theoretical study of structure-property relationships, further paradigms of NIR-II J-aggregates remain scarce due to the lack of study on aggregated fluorophores with slip-stacked fashion. In this effort, how to utilize the specific molecular structure to form slip-stacked packing motifs with J-type aggregated exciton coupling is emphatically elucidated. First, several molecular regulating strategies to achieve NIR-II J-aggregates containing intermolecular interactions and external conditions are positively summarized and deeply analyzed. Then, the recent reports on J-aggregates for NIR-II bioimaging and theranostics are systematically summarized to provide a clear reference and direction for promoting the development of NIR-II organic fluorophores. Eventually, the prospective efforts on ameliorating and promoting NIR-II J-aggregates to further clinical practices are outlined.

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Many fluorophores, such as indocyanine green (ICG), have poor photostability and low photothermal efficiency hindering their wide application in photoacoustic (PA) tomography. In the present study, a supramolecular assembly approach was used to develop the hybrid nanoparticles (Hy NPs) of ICG and porous silicon (PSi) as a novel contrast agent for PA tomography. ICG was assembled on the PSi NPs to form J-aggregates within 30 min. The Hy NPs presented a red-shifted absorption, improved photothermal stability, and enhanced PA performance. Furthermore, 1-dodecene (DOC) was assembled into the NPs as a 'nanospacer', which enhanced non-radiative decay for increased thermal release. Compared to the Hy NPs, adding DOC into the Hy NPs (DOC-Hy) increased the PA signal by 83%. Finally, the DOC-Hy was detectable in PA tomography at 1.5 cm depth in tissue phantom even though its concentration was as low as 6.25 µg/mL, indicating the potential for deep tissue PA imaging.

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Developing molecular fluorophores with enhanced fluorescence in aggregate state for the second near-infrared (NIR-II) imaging is highly desirable but remains a tremendous challenge due to the lack of reliable design guidelines. Herein, we report an aromatic substituent strategy to construct highly bright NIR-II J-aggregates. Introduction of electron-withdrawing substituents at 3,5-aryl and meso positions of classic boron dipyrromethene (BODIPY) skeleton can promote slip-stacked J-type arrangement and further boost NIR-II fluorescence of J-aggregates via increased electrostatic repulsion and intermolecular hydrogen bond interaction. Notably, NOBDP-NO2 with three nitro groups (-NO2 ) shows intense NIR-II fluorescence at 1065 nm and high absolute quantum yield of 3.21 % in solid state, which can be successfully applied in bioimaging, high-level encoding encryption, and information storage. Moreover, guided by this electron-withdrawing substituent strategy, other skeletons (thieno-fused BODIPY, aza-BODIPY, and heptamethine cyanine) modified with -NO2 are converted into J-type aggregates with enhanced NIR-II fluorescence, showing great potential to convert aggregation caused emission quenching (ACQ) dyes into brilliant J-aggregates. This study provides a universal method for construction of strong NIR-II emissive J-aggregates by rationally manipulating molecular packing and establishing relationships among molecular structures, intermolecular interactions, and fluorescence properties.

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