Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, we transformed two ionic ICG derivatives into neutral merocyanines (mCy) to achieve much enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes showed similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000 nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrated that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics. This article is protected by copyright. All rights reserved.

Brightness Strategies toward NIR-II Emissive Conjugated Materials: Molecular Design, Application, and Future Prospects.

Recent advances have been made in second near-infrared (NIR-II) fluorescence bioimaging and many related applications because of its advantages of deep penetration, high resolution, minimal invasiveness, and good dynamic visualization. To achieve high-performance NIR-II fluorescence bioimaging, various materials and probes with bright NIR-II emission have been extensively explored in the past few years. Among these NIR-II emissive materials, conjugated polymers and conjugated small molecules have attracted wide interest due to their native biosafety and tunable optical performance. This review summarizes the brightness strategies available for NIR-II emissive conjugated materials and highlights the recent developments in NIR-II fluorescence bioimaging. A concise, detailed overview of the molecular design and regulatory approaches is provided in terms of their high brightness, long wavelengths, and superior imaging performance. Then, various typical cases in which bright conjugated materials are used as NIR-II probes are introduced by providing step-by-step examples. Finally, the current problems and challenges associated with accessing NIR-II emissive conjugated materials for bright NIR-II fluorescence bioimaging are briefly discussed, and the significance and future prospects of these materials are proposed to offer helpful guidance for the development of NIR-II emissive materials.

A Nanographene-Porphyrin Hybrid for Near-Infrared-Ii Phototheranostics.

Photoacoustic imaging (PAI)-guided photothermal therapy (PTT) in the second near-infrared (NIR-II, 1000-1700 nm) window has been attracting attention as a promising cancer theranostic platform. Here, it is reported that the π-extended porphyrins fused with one or two nanographene units (NGP-1 and NGP-2) can serve as a new class of NIR-responsive organic agents, displaying absorption extending to ≈1000 and ≈1400 nm in the NIR-I and NIR-II windows, respectively. NGP-1 and NGP-2 are dispersed in water through encapsulation into self-assembled nanoparticles (NPs), achieving high photothermal conversion efficiency of 60% and 69%, respectively, under 808 and 1064 nm laser irradiation. Moreover, the NIR-II-active NGP-2-NPs demonstrated promising photoacoustic responses, along with high photostability and biocompatibility, enabling PAI and efficient NIR-II PTT of cancer in vivo.

Organo-Ptii Complexes for Potent Photodynamic Inactivation of Multi-Drug Resistant Bacteria and the Influence of Configuration.

PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded PtII PSs. The cis-isomer (cis-BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm-2) and 100 nM (18 J cm-2), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm-2) and 1.50 µM (18 J cm-2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.

Ultra-efficient delivery of CRISPR/Cas9 using ionic liquid conjugated polymers for genome editing-based tumor therapy.

Emerging CRISPR-Cas9 systems can rebuild DNA sequences in the genome in a spatiotemporal manner, offering a magic tool for biological research, drug discovery, and gene therapy. However, low delivery efficiency remains a major roadblock hampering the wide application of CRISPR-Cas9 gene editing talent. Herein, ionic liquid-conjugated polymers (IL-CPs) are explored as efficient platforms for CRISPR-Cas9 plasmid delivery and in vivo genome editing-based tumor therapy. Via molecular screening of IL-CPs, IL-CPs integrated with fluorination monomers (PBF) can encapsulate plasmids into hybrid nanoparticles and achieve over 90% delivery efficiency in various cells regardless of serum interference. In vitro and in vivo experiments demonstrate that PBF can mediate Cas9/PLK1 plasmids for intracellular delivery and therapeutic genome editing in tumor, achieving efficient tumor suppression. This work provides a new tool for safe and efficient CRISPR-Cas9 delivery and therapeutic genome editing, thus opening a new avenue for the development of ionic liquid polymeric vectors for genome editing and therapy.

Bacterially synthesized superfine tellurium nanoneedles as an antibacterial and solar-thermal still for efficient purification of polluted water.

Bacterial biosynthesis of nanomaterials has several advantages (e.g., reduced energy inputs, lower cost, negligible environmental pollution) compared with traditional approaches. Various nanomaterials have been produced by bacteria. However, reports on using the bacterial biosynthesis of nanomaterials for applications with solar-thermal agents are scarce due to their narrow optical absorption. Herein, for the first time, we proposed a bacterial biosynthesis of broad-absorbing tellurium nanoneedles and demonstrated their effectiveness for solar-thermal evaporation and antibacterial applications. By simple biosynthesis within bacteria (Shewanella oneidensis MR-1), tellurium nanoneedles achieved a superfine configuration with a length-to-diameter ratio of nearly 20 and broad-spectrum absorbance. After integrating tellurium nanoneedles into a porous polyvinyl-alcohol scaffold, a solar-thermal still named TSAS-3 realized a high evaporation rate of 2.25 kg m-2 h-1 and solar-thermal conversion efficiency of 81% upon 1-Sun illumination. Based on these unique properties, the scaffold displayed good performances in seawater desalination, multiple wastewater treatment, and antibacterial applications. This work provides a simple and feasible strategy for the use of microbial-synthesized nanomaterials in solar-driven water purification and antibacterial applications.

Recent strategies for evoking immunogenic Pyroptosis in antitumor immunotherapy.

Pyroptosis is a specific type of programmed cell death (PCD) characterized by distinct morphological changes, including cell swelling, membrane blebbing, DNA fragmentation, and eventual cell lysis. Pyroptosis is closely associated with human-related diseases, such as inflammation and malignancies. Since the initial observation of pyroptosis in Shigella flexneri-infected macrophages more than 20 years ago, various pyroptosis-inducing agents, including ions, small molecules, and biological nanomaterials, have been developed for tumor treatment. Given that pyroptosis can activate the body's robust immune response against tumor and promote the formation of the body's long-term immune memory in tumor treatment, its status as a type of immunogenic cell death is self-evident. Therefore, pyroptosis should be used as a powerful anti-tumor strategy. However, there still is a lack of a comprehensive summary of the most recent advances in pyroptosis-based cancer therapy. Therefore, it is vital to fill this gap and inspire future drug design to better induce tumor cells to undergo pyroptosis to achieve advanced anti-tumor effects. In this review, we summarize in detail the most recent advances in triggering tumor cell immunogenic pyroptosis for adequate tumor clearance based on various treatment modalities, and highlight material design and therapeutic advantages. Besides, we also provide an outlook on the prospects of this emerging field in the next development.

Dual Activation of Calcium Channels Using Near-Infrared Responsive Conjugated Oligomer Nanoparticles for Precise Regulation of Blood Glucose Homeostasis.

The rarity of efficient tools with spatiotemporal resolution and biocompatibility capabilities remains a major challenge for further progress and application of signaling manipulation. Herein, biomimetic conjugated oligomeric nanoparticles (CM-CONs) were developed to precisely modulate blood glucose homeostasis via the two-pronged activation of calcium channels. Under near-infrared (NIR) laser irradiation, CM-CONs efficiently generate local heat and reactive oxygen species (ROS), thereby simultaneously activating thermosensitive transient receptor potential V1 (TRPV1) and ROS-sensitive transient receptor potential A1 (TRPA1) calcium channels in small intestinal endocrine cells. The activation of the channels mediates inward calcium flow and then promotes glucagon-like peptide (GLP-1) secretion. Both in vitro and in vivo studies indicate that CM-CONs effectively regulate glucose homeostasis in diabetic model mice upon NIR light irradiation. This work develops a two-pronged attack strategy for accurately controlling blood glucose homeostasis, holding great prospects in the treatment for diabetes.

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-II Photo-Immunotherapy of Metastatic Tumor.

Massive efforts have been concentrated on the advance of eminent near-infrared (NIR) photothermal materials (PTMs) in the NIR-II window (1000-1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-II-responsive organic PTMs was explored, and their photothermal conversion efficiencies (PCEs) still remain relatively low. Herein, donor-acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-II window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-II absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-II light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-II window, without any side-effect. Moreover, by combining with PD-1 antibody, the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-II window, offering a new horizon in developing radical-characteristic NIR-II photothermal materials.

NIR-II Regulation of Mitochondrial Potassium Channel with Dual-Targeted Conjugated Oligomer Nanoparticles for Efficient Cancer Theranostics In Vivo.

Cell fate can be efficiently modulated by switching ion channels. However, the precise regulation of ion channels in cells, especially in specific organelles, remains challenging. Herein, biomimetic second near-infrared (NIR-II) responsive conjugated oligomer nanoparticles with dual-targeted properties are designed and prepared to modulate the ion channels of mitochondria to selectively kill malignant cells in vivo. Upon 1060 nm laser irradiation, the mitochondria-located nanoparticles photothermally release a specific ion inhibitor of the potassium channel via a temperature-sensitive liposome, thus altering the redox balance and pathways of mitochondria. NIR-II responsive nanoparticles can effectively regulate the potassium channels of mitochondria and fully suppress tumor growth. This work provides a new modality based on the NIR-II nanoplatform to regulate ion channels in specific organelles and proposes an effective therapeutic mechanism for malignant tumors.

Selenium-integrated conjugated oligomer nanoparticles with high photothermal conversion efficiency for NIR-II imaging-guided cancer phototheranostics in vivo.

Second near-infrared (NIR-II) fluorescence imaging in the range of 1000-1700 nm has great prospects for in vivo imaging and theranostics monitoring. At present, few NIR-II probes with theranostics properties have been developed, especially the high-performance organic theranostics material remains underexploited. Herein, we demonstrate a selenium (Se)-tailoring method to develop high-efficient NIR-II imaging-guided material for in vivo cancer phototheranostics. Via Se-tailoring strategy, conjugated oligomer TPSe-based nanoparticles (TPSe NPs) achieve bright NIR-II emission up to 1400 nm and exhibit a relatively high photothermal conversion efficiency of 60% with good stability. Moreover, the TPSe NPs demonstrate their photothermal ablation of cancer cells in vitro and tumor in vivo with the guidance of NIR-II imaging. It is worth noting that the TPSe NPs have good biocompatibility without obvious side effects. Thus, this work provides new insight into the development of NIR-II theranostics agents.

NIR-II fluorescence and PA imaging guided activation of STING pathway in photothermal therapy for boosting cancer immunotherapy by theranostic thermosensitive liposomes.

Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cell (DC) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost the adaptive anti-tumor immunity of photothermal immunotherapy and to achieve multiple bioimaging modalities in a real-time manner. PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cell maturation and T cell recruitment. Moreover, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.

Recent Progress of Preparation Strategies in Organic Nanoparticles for Cancer Phototherapeutics.

Phototherapy has the advantages of being a highly targeted, less toxic, less invasive, and repeatable treatment, compared with conventional treatment methods such as surgery, chemotherapy, and radiotherapy. The preparation strategies are significant in order to determine the physical and chemical properties of nanoparticles. However, choosing appropriate preparation strategies to meet applications is still challenging. This review summarizes the recent progress of preparation strategies in organic nanoparticles, mainly focusing on the principles, methods, and advantages of nanopreparation strategies. In addition, typical examples of cancer phototherapeutics are introduced in detail to inform the choice of appropriate preparation strategies. The relative future trend and outlook are preliminarily proposed.

Dual-Pronged Attack: pH-Driven Membrane-Anchored NIR Dual-Type Nano-Photosensitizer Excites Immunogenic Pyroptosis and Sequester Immune Checkpoint for Enhanced Prostate Cancer Photo-Immunotherapy.

Prostate cancer (PCa) is a frustrating immunogenic "cold" tumor and generally receives unsatisfied immunotherapy outcomes in the clinic. Pyroptosis is an excellent immunogenic cell death form that can effectively activate the antitumor immune response, promote cytotoxic T-lymphocyte infiltration, and convert tumors from "cold" to "hot." However, the in vivo application of pyroptosis drugs is seriously limited, and the upregulation of tumor PD-L1 caused by photo-immunotherapy further promotes immune escape. Herein, a new nano-photosensitizer (YBS-BMS NPs-RKC) with pH-response integrating immunogenic pyroptosis induction and immune checkpoint blockade is developed. The pH-responsive polymer equipped with the cell membrane anchoring peptide RKC is used as the carrier and further encapsulated with the near-infrared-activated semiconductor polymer photosensitizer YBS and a PD-1/PD-L1 complex small molecule inhibitor BMS-202. The pH-driven membrane-anchoring and pyroptosis activation of YBS-BMS NPs-RKC is clearly demonstrated. In vitro and in vivo studies have shown that this dual-pronged therapy stimulates a powerful antitumor immune response to suppress primary tumor progression and evokes long-term immune memory to inhibit tumor relapse and metastasis. This work provides an effective self-synergistic platform for PCa immunotherapy and a new idea for developing more biocompatible photo-controlled pyroptosis inducers.

Organic Optoelectronic Materials: A Rising Star of Bioimaging and Phototherapy.

Recently, many organic optoelectronic materials (OOMs), especially those used in organic light-emitting diodes (OLEDs), organic solar cells (OSCs), and organic field-effect transistors (OFETs), are explored for biomedical applications including imaging and photoexcited therapies. In this review, recently developed OOMs for fluorescence imaging, photoacoustic imaging, photothermal therapy, and photodynamic therapy, are summarized. Relationships between their molecular structures, nanoaggregation structures, photophysical mechanisms, and properties for various biomedical applications are discussed. Mainly four kinds of OOMs are covered: thermally activated delayed fluorescence materials in OLEDs, conjugated small molecules and polymers in OSCs, and charge-transfer complexes in OFETs. Based on the OOMs unique optical properties, including excitation light wavelength and exciton dynamics, they are respectively exploited for suitable biomedical applications. This review is intended to serve as a bridge between researchers in the area of organic optoelectronic devices and those in the area of biomedical applications. Moreover, it provides guidance for selecting or modifying OOMs for high-performance biomedical uses. Current challenges and future perspectives of OOMs are also discussed with the hope of inspiring further development of OOMs for efficient biomedical applications.

Anti-Quenching NIR-II J-Aggregates of Benzo[c]thiophene Fluorophore for Highly Efficient Bioimaging and Phototheranostics.

Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used to construct long-wavelength NIR-II emitters as their optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, their wide applications in the NIR-II fluorescence imaging are impeded by the limited varieties of J-type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) with anti-quenching effect is reported for highly efficient NIR-II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation-induced emission (AIE) property for conquering the self-quenching issue of the J-type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR-II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole-body blood vessel and imaging-guided phototherapy results verify that BT6 NPs are excellent agent for NIR-II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR-II J-aggregates with precisely manipulated anti-quenching properties for highly efficient biomedical applications.

Plasmoelectric Potential in Plasmon-Mediated Electrochemistry.

Plasmon-mediated chemical reactions have attracted intensive research interest as a means of achieving desirable reaction yields and selectivity. The energetic charge carriers and elevated local temperature induced by the nonradiative decay of surface plasmons are thought to be responsible for improving reaction outcomes. This study reports that the plasmoelectric potential is another key contributor in plasmon-mediated electrochemistry. Additionally, we disclose a convenient and reliable method for quantifying the specific contributions of the plasmoelectric potential, hot electrons, and photothermal heating to the electroreduction of oxygen at the plasmonic Ag electrode, revealing that the plasmoelectric potential is the dominating nonthermal factor under short-wavelength illumination and moderate electrode bias. This work elucidates novel mechanistic understandings of plasmon-mediated electrochemistry, facilitating high-performance plasmonic electrocatalyst design optimization.

Innovative probes with aggregation-induced emission characteristics for sensing gaseous signaling molecules.

Diseases are often accompanied by abnormal expression of gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S). Sensing these gaseous markers is thus important for identification and investigation of pathological processes. In contrast to conventional approaches, such as electrochemical, chromatographical methods, etc., optical imaging shows merits including high sensitivity, good spatiotemporal resolution, and ideal selectivity. Especially, optical molecular probes with aggregation-induced emission (AIE) properties have good potential for bio-detection since they show maintained optical signals in the aggregated state. Recently, many AIE molecular probes have been developed for imaging disease-related gaseous signaling molecules. Generally, these probes recognize the analytes through turn-on or ratiometric approaches. This review summarizes the recent progress in organic probes with AIE properties for sensing gaseous markers and relative disease diagnosis applications. Based on the types of analytes, the probes are divided into three groups: NO, CO and H2S sensors. Molecular designs and sensing mechanisms of these AIE probes are highlighted. Their gaseous signaling molecules detection applications at cellular and animal levels are presented. Finally, some existing problems and future promising development directions are discussed with the hope to inspire further developments of AIE probes for precise disease diagnosis.

From Materials to Devices: Rationally Designing Solar Steam System for Advanced Applications.

Solar-driven water vaporization for freshwater production attracts significant interest due to its potential for solving global water scarcity problems. In this review, the recent development of management strategies via diverse rational designs in terms of light, thermal, water, and anti-salt fouling for enhancement of overall vaporization efficiency, is summarized. For device design, a host-guest concept is raised for clearly elaborating the detailed function and interaction between the solar-thermal material and the substrates. In addition, the rising technologies derived from solar vaporization, such as energy generation, photocatalysis, dehumidification, salt harvesting, sterilization, and biofuel production, are also highlighted. This review provides a new horizon toward the development of solar technologies and practical applications.

Bright Near-Infrared π-Conjugated Oligomer Nanoparticles for Deep-Brain Three-Photon Microscopy Excited at the 1700 nm Window in Vivo.

The development of three-photon fluorophores with 1700 nm excitation is pressingly desirable for in vivo imaging of tissue resided deep inside the brain. Herein, we report a designed and synthesized fluorescent molecule (OFET) for in vivo mouse brain imaging with three-photon microscopy at a record imaging depth. The OFET molecule has a relatively high fluorescence brightness and has a near-infrared (NIR) maximum emission at 820 nm after integrating as water-dispersible nanoparticles (OEFT NPs). Under 1720 nm excitation, OFET NPs show a large three-photon action cross-section of 1.06 × 10-82 cm6 s2/photon2, which is more than twice that of the commonly used sulforhodamine 101 (SR101) dye. Benefiting from the high tissue penetration depths for both the long excitation in the second NIR window of 1720 nm and the emission wavelength in the first NIR window of 820 nm, a high brightness, and a large action cross-section of three-photon, OFET NPs have good deep-brain imaging performance. Brain vasculatures of a mouse located at a depth of 1696 µm can be clearly resolved in vivo. With no observable cytotoxicity even in a high concentration, the present OFET NPs suggest that fluorescent π-conjugated oligomers are of great potential in high-resolution 3PM imaging of in vivo deep-tissue.