Near-infrared II Research Articles

Side Chain Phenyl Isomerization‐Induced Spatial Conjugation for Achieving Efficient Near‐Infrared II Phototheranostic Agents

AbstractThe contradiction of near‐infrared II (NIR‐II) emission and photothermal effects limits the development of phototheranostic agents (PTAs) in many emerging cutting‐edge applications. Organic aggregates present a promising opportunity for the balance of competitive relaxation processes through the manipulation of molecular structure and packing. Herein, side chain phenyl isomerization‐induced spatial conjugation was proposed for constructing A‐D‐A type NIR‐II PTAs with simultaneous enhancement of fluorescence brightness and photothermal properties. Three pairs of mutually isomeric fluorophores, whose phenyls respectively located at the outside (o‐series) and inside (i‐series) of the side chain, were designed and synthesized. The positional isomerization of the phenyl endows the o‐series crystals with strong spatial conjugation between the phenyl group on the side chain and the backbone, as well as interlocked planar network, which is different to that observed in the i‐series. Thus, all o‐series nanoparticles (NPs) exhibit red‐shifted absorption, enhanced NIR‐II emission, and superior photothermal properties than their i‐series counterparts. A prominent member of the o‐series, o‐ITNP NPs, demonstrated efficacy in facilitating NIR‐II angiography, tumor localization, and NIR‐II imaging‐guided tumor photothermal therapy. The success of this side chain phenyl isomerization strategy paves the way for precise control of the aggregation behavior and for further development of efficient NIR‐II PTAs.

Side Chain Phenyl Isomerization-Induced Spatial Conjugation for Achieving Efficient Near-Infrared II Phototheranostic Agents.

The contradiction of near-infrared II (NIR-II) emission and photothermal effects limits the development of phototheranostic agents (PTAs) in many emerging cutting-edge applications. Organic aggregates present a promising opportunity for the balance of competitive relaxation processes through the manipulation of molecular structure and packing. Herein, side chain phenyl isomerization-induced spatial conjugation was proposed for constructing A-D-A type NIR-II PTAs with simultaneous enhancement of fluorescence brightness and photothermal properties. Three pairs of mutually isomeric fluorophores, whose phenyls respectively located at the outside (o-series) and inside (i-series) of the side chain, were designed and synthesized. The positional isomerization of the phenyl endows the o-series crystals with strong spatial conjugation between the phenyl group on the side chain and the backbone, as well as interlocked planar network, which is different to that observed in the i-series. Thus, all o-series nanoparticles (NPs) exhibit red-shifted absorption, enhanced NIR-II emission, and superior photothermal properties than their i-series counterparts. A prominent member of the o-series, o-ITNP NPs, demonstrated efficacy in facilitating NIR-II angiography, tumor localization, and NIR-II imaging-guided tumor photothermal therapy. The success of this side chain phenyl isomerization strategy paves the way for precise control of the aggregation behavior and for further development of efficient NIR-II PTAs.

Molecular engineering of Au25(SG)18 nanoclusters at the single cluster level to brighten their NIR-II fluorescence.

Au25(SG)18 (SG: glutathione) nanoclusters, characterized by their atomically precise structures, exhibit near-infrared II (NIR-II) fluorescence emission and excellent biocompatibility, making them highly promising for imaging applications. However, their comparatively low photoluminescence quantum yield (QY) in aqueous solutions limits their further development. In this study, taking advantage of the molecular-like properties of Au25(SG)18 nanoclusters, we employ a Schiff base reaction to improve their NIR-II emission for the first time. The formation of a Schiff base chemical bond restricts intramolecular motion of surface ligands on the Au25(SG)18 nanoclusters, reduces the nonradiative rate, and increases the radiative transition rate. Consequently, the luminescence quantum yield of PDA-Au25(SG)18 (PDA: 2,6-pyridinedicarboxaldehyde) nanoclusters is enhanced to 3.26%. Moreover, the reaction between amino and aldehyde groups occurs at the single cluster level, ensuring that these PDA-Au25(SG)18 nanoclusters remain discrete with an ultrasmall size of 2.6 nm, facilitating rapid excretion via the renal system and also showing excellent photostability and biocompatibility.

Near-Infrared-II-Activated Transition Metal(II)-Coordinated Ligand Radical Primes Robust Anticancer Immunity.

Photoactivatable metallodrugs combining tumor cell eradication and immune stimulation hold immense promise for targeted cancer therapy. However, limitations such as oxygen dependence, narrow visible light responsiveness, and poor immunogenicity hinder their efficacy in deep solid tumors with hypoxic and immunosuppressive microenvironments. Herein, we present a novel design strategy for transition metal(II)-coordinated ligand radicals exhibiting intense near-infrared-II (NIR-II) absorption, unique endoplasmic reticulum-targeting capability, and oxygen-independent photothermal performance, effectively addressing these constraints. Proof-of-concept results demonstrate the potent efficacy of our cobalt(II)-coordinated ligand radical (BPDP-Co) in inducing highly immunogenic pyroptosis in tumor cells under both normoxic and severe hypoxic conditions upon 1064 nm laser irradiation. This NIR-II activation triggers the release of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, fueling a robust antitumor immune response. In vivo studies demonstrate that treatment with BPDP-Co/NIR-II significantly inhibited 4T1 tumor growth in BALB/c mice with a high inhibitory rate of 85.7%, highlighting its therapeutic potential in tumor immunotherapy.

Highly Stable Near-Infrared II Luminescent Diradicaloids for Cancer Phototheranostics.

Near-infrared II (NIR-II) phototheranostic agents have become prominent agents for the early diagnosis and precise treatment of cancer. Organic open-shell diradicaloids with distinct structure and narrow band gap are promising candidates for phototherapeutic agents due to their strong spin-coupling effect and NIR light-harvesting capacity. However, achieving stable and efficient NIR-II luminescent diradicaloids is crucial yet rather challenging considering their high chemical reactivity and self-absorption. Herein, two highly stable NIR-II luminescent diradicaloids, 2PhNVDPP and PhNVDPP, were successfully fabricated by employing an acceptor planarization/π-conjugation extension and donor rotation strategy. After encapsulation into water-dispersible nanoparticles (NPs), 2PhNVDPP NPs exhibit NIR-II luminescence, high PCE of 53%, and improved photo/heat stability. In vivo experiments with 2PhNVDPP NPs demonstrated the clear visualization of blood vessels and tumors, as well as the successful NIR-II imaging-guided photothermal ablation of tumors. This study not only develops a pioneering stable diradicaloid phototherapeutic agent with NIR-II luminescence but also provides a unique perspective for the effectiveness of multimodal anticancer therapy.

Biomimetic Dual‐Driven Heterojunction Nanomotors for Targeted Catalytic Immunotherapy of Glioblastoma

AbstractThe existence of the blood–brain barrier (BBB) and the characteristics of the immunosuppressive microenvironment in glioblastoma (GBM) present significant challenges for targeted GBM therapy. To address this, a biomimetic hybrid cell membrane‐modified dual‐driven heterojunction nanomotor (HM@MnO2‐AuNR‐SiO2) is proposed for targeted GBM treatment. These nanomotors are designed to bypass the BBB and target glioma regions by mimicking the surface characteristics of GBM and macrophage membranes. More importantly, the MnO2‐AuNR‐SiO2 heterojunction structure enables dual‐driven propulsion through near‐infrared‐II (NIR‐II) light and oxygen bubbles, allowing effective treatment at deep tumor sites. Meanwhile, the plasmonic AuNR‐MnO2 heterostructure facilitates the separation of electron–hole pairs and generates reactive oxygen species (ROS), inducing immunogenic tumor cell death under NIR‐II laser irradiation. Furthermore, MnO2 in the tumor microenvironment reacts to release Mn2+ ions, activating the cGAS‐STING pathway and enhancing antitumor immunity. In vitro and in vivo experiments demonstrate that these dual‐driven biomimetic nanomotors achieve active targeting and deep tumor infiltration, promoting M1 macrophage polarization, dendritic cell maturation, and effector T‐cell activation, thereby enhancing GBM catalysis and immunotherapy through ROS production and STING pathway activation.

Near‐Infrared II AIE Luminogens with Mitochondria‐Targeting Characteristics for Combinational Phototherapies of Breast Tumors Through Synergistic Cell Apoptosis and Pyroptosis

AbstractConventional photosensitizers for tumor phototherapy are greatly limited by their reliance on a single‐cell death process, leading to insufficient therapeutic effects and restricted biomedical applications. To address these limitations, multifunctional fluorophores, BTA and BTB, are designed based on an electron donor‐π‐acceptor system. By adjusting the strength of the intramolecular charge transfer through varying electron‐donating moieties, their optical properties are tailored. BTA emits bright near‐infrared II (NIR‐II) fluorescence and exhibits typical aggregation‐induced emission (AIE) characteristics, a large Stokes shift (>250 nm), good photostability, satisfactory biocompatibility, and remarkable mitochondria‐targeting capabilities. Notably, it demonstrates potent photodynamic and photothermal properties. BTA as an effective photosensitizer and a photothermal agent, generates various cytotoxic Type I and II reactive oxygen species and photothermal energy to effectively destroy tumor cell mitochondria and suppress tumor growth. Importantly, the molecular mechanisms underlying combination phototherapy are elucidated, revealing that it induces synergistic cell apoptosis and pyroptosis. These results highlight the potential of multifunctional AIE materials with bright NIR‐II fluorescence and mitochondria‐targeting characteristics for the synergistic phototherapy of breast tumors, offering new insights for future therapeutic developments.

Electrostatic Assembly of Gold Nanoclusters in Reverse Emulsion Enabling Nanoassemblies with Tunable Structure and Size for Enhanced NIR-II Fluorescence Imaging.

The precise control of the assembly structure and size of gold nanoclusters (AuNCs) can potentially amplify their near-infrared II (NIR-II) fluorescence imaging and targeting properties. However, the conventional electrostatic assembly of AuNCs and charged molecules faces challenges in balancing the inherent electrostatic repulsions among charged units and regulating the diffusion of assembly units. These difficulties limit precise control over assembly size and structure, along with limited options for coassembled molecules, thereby restricting imaging properties and targeting capability. To circumvent this challenge, we developed a reverse emulsion-confined electrostatic assembly method. This technique efficiently constructs AuNC nanoassemblies with diverse coassembled molecules, allowing for the fine-tuning of assembly size and structure, including both core-satellite and homogeneous AuNC nanoassemblies. The development of two distinct nanoassemblies can be partially attributed to the varying diffusive rates of AuNCs or the AuNCs/polymer complex within the fused emulsion droplets. This variance arises from steric hindrances encountered during the emulsion fusion process. Interestingly, core-satellite nanoassemblies exhibit the strongest NIR-II fluorescence enhancement. Finally, the introduction of a hyaluronic acid coating on the surfaces of nanoassemblies with varying sizes enables the nanoprobes to achieve enhanced lymph node imaging through size modulation and macrophage targeting, which are used for surgical navigation to remove lymph node metastases. We envision that this self-assembly strategy can be extended to a wide range of electrostatic assembly systems for the development of multicomponent functional materials.

A tumor Microenvironment-triggered protein-binding Near-infrared-II Theranostic nanoplatform for Mild-Temperature photothermal therapy

Photothermal therapy (PTT) has gained significant attention as a non-invasive treatment in clinical oncology. However, the translation of PTT into clinical practice remains constrained by three fundamental limitations: acquired thermal tolerance in tumor cells, restricted light penetration depth in biological matrices, and insufficient therapeutic outcomes from single-modality treatment. To address these issues, a strategy for forming in situ complexes between near-infrared-II (NIR-II) photothermal agents and proteins is developed, aimed at damaging protein conformation and enhancing PTT effectiveness. We developed a nanoplatform called PCy-SF, consisting of the NIR-II photothermal polymer (PCy) and sorafenib (SF). PCy-SF responds to the tumor microenvironment (TME), specifically releasing Cy-CHO and sorafenib from the assemblies. The released Cy-CHO covalently binds to proteins, forming Cy-Protein complexes that activate NIR-II fluorescence, facilitating NIR-II imaging-guided photothermal therapy. Concurrently, the released SF intensifies microvascular damage, synergizing with PTT for enhanced therapeutic efficacy. Notably, PCy-SF induces a strong anticancer immune response, effectively suppressing tumor recurrence and metastasis. This study introduces a promising protein deactivation strategy for achieving mild-temperature PTT, offering broader applicability of PTT and insights for sensitizing tumors to photothermal therapy. Together, this innovative approach combining NIR-II photothermal agents with protein complexation and a responsive nanoplatform enhances PTT precision and efficacy, demonstrating significant potential in the field of cancer nanomedicine.

A Multifunctional Low-Temperature Photothermal Nanomedicine for Melanoma Treatment via the Oxidative Stress Pathway Therapy.

Melanoma is a highly aggressive and dangerous malignant skin tumor and there is an urgent need to develop effective therapeutic approaches against melanoma. The main objective of this study was to construct a multifunctional nanomedicine (GNR@PEG-Qu) to investigate its therapeutic effect on melanoma from the oxidative stress pathway. First, the nanomedicine GNR@PEG-Qu was synthesized and characterized, and its photothermal and antioxidant properties were confirmed. In addition, in vivo imaging capabilities were observed. Finally, the tumor inhibitory effects of GNR@PEG-Qu in vivo and in vitro as well as its biosafety were observed. GNR@PEG-Qu shows good photothermal and anti-oxidation properties. Following exposure to 1064 nm laser irradiation in the second near-infrared II (NIR-II) window, GNR@PEG-Qu shows anti-tumor ability through low-temperature photothermal therapy (PTT) adjuvant drug chemotherapy. GNR@PEG-Qu makes full use of the antioxidant capacity of quercetin, reduces ROS levels in melanoma, alleviates oxidative stress state, and achieves "oxidative stress avoidance" at the tumor site. Quercetin can also downregulate the expression of the heat shock protein Hsp70, which will improve the thermal sensitivity of the tumor site and enhance the efficacy of low-temperature PTT. GNR@PEG-Qu nanoagent exhibits synergistic treatment and high tumor inhibition effects, which is a promising strategy developed to achieve oxidative stress avoidance and synergistic therapy of melanoma using quercetin (Qu)-coated gold nanorod (GNR@PEG).

Neutrophil-Mimetic Upconversion Photosynthetic Nanosystem Derived from Microalgae for Targeted Treatment of Thromboembolic Stroke.

Thromboembolic stroke constitutes the majority of brain strokes, resulting in elevated mortality and morbidity rates, as well as significant societal and economic burdens. Although intravenous thrombolysis serves as the standard clinical treatment, its narrow therapeutic window and the inflammatory response induced by tissue plasminogen activator (tPA) administration limit its efficacy. In the initial stages of stroke, the abrupt cessation of blood flow leads to an energy metabolism disorder, marked by a substantial decrease in adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, causing irreversible damage to neural cells. In this study, we introduce a neutrophil-mimetic, microalgae-derived upconversion photosynthetic nanosystem designed for targeted treatment of thromboembolic stroke. This system features upconversion nanoparticles coated with a thylakoid membrane and wrapped in an activated neutrophil membrane, further decorated with ROS-responsive thrombolytic tPA on its surface. The neutrophil-mimetic design facilitates high targeting specificity and accumulation at the thrombus site after intravenous administration. Upon exposure to elevated levels of reactive oxygen species (ROS) at the thrombus location, the nanosystem promptly demonstrated potent thrombolytic efficacy through the surface-modified tPA. Furthermore, near-infrared II (NIR-II) laser irradiation activated the generation of ATP and NADPH, which inhibited inflammatory cell infiltration, platelet activation, oxidative stress, and neuronal injury. This constructed nanoplatform not only showcases exceptional targeting efficiency at the stroke site and controllable release of the thrombolytic agent but also facilitates ATP/NADPH-mediated thrombolytic, anti-inflammatory, antioxidative stress, and neuroprotective effects. Additionally, it offers valuable insights into the potential therapeutic applications of microalgae-based derivatives in managing thromboembolic stroke.

Bovine serum albumin framed activatable NIR AIE photosensitizer for targeted tumor therapy

Organic near-infrared (NIR) photosensitizers (PS) largely facilitate photodynamic therapy (PDT). To overcome aggregation induced quenching and diminishment of reactive oxygen species (ROS) generation capability of NIR-PS, aggregation-induced emission (AIE) effect groups have been introduced to generate NIR AIE photosensitizers. However, currently reported NIR AIE photosensitizers all take “always-on” activity that may cause systemic phototoxic side effects. Tumor microenvironment activatable NIR AIE photosensitizers have not been reported. Here we develop an activatable NIR AIE PSnanoparticle (a-NA-PSNP) for near-infrared-II (NIR-II) fluorescence (FL) imaging-guided PDT under 808 nm excitation. NIR AIE photosensitizer (N-PS) is designed and frames with cysteine (Cys)/glutathione (GSH) responsive charge transfer complex (CTC) in bovine serum albumin (BSA) to obtain a-NA-PSNP. With the aggregated state in BSA, N-PS shows high quantum yield with good photostability. As an energy acceptor, CTC quenchs NIR-II fluorescence and ROS production capability of a-NA-PSNP in normal cells and tissues. CTC is decomposed in response to tumor microenvironment Cys/GSH, therefore recovers NIR-II fluorescence of a-NA-PSNP and efficiently generates ROS under 808 nm light irradiation. The depletion of Cys/GSH also regulates tumor intracellular reductive environment to further facilitate PDT. Both in vitro and in vivo results confirmed the tumor microenvironment selective and efficient activation of a-NA-PSNP, indicating its potential in cancer therapy.

Carrier-Free Biomimetic Organic Nanoparticles with Super-High Drug Loading for Targeted NIR-II Excitable Triple-Modal Bioimaging and Phototheranostics.

Multimodal near-infrared II (NIR-II) theranostics combined with nanotechnology have emerged as promising treatments for cancer due to their noninvasive and high spatiotemporal nature. Traditional NIR-II theranostics typically comprise useless and massive inert carriers, resulting in low drug loading capacity, reduced therapeutic effects, and potential biotoxicity. To overcome these limitations, this work reports carrier-free NIR-II theranostics simultaneously with high drug loading capacity and multimodal NIR-II imaging capabilities for cancer phototheranostics in the NIR-II window. Carrier-free BTA nanoparticles (NPs) are prepared by self-assembling the NIR-II responsive conjugated oligomer BTA without adding coating agents; these NPs exhibited 100% drug loading and high-performance NIR-II theranostic capabilities. Cancer cell membranes are camouflaged on carrier-free BTA NPs to provide homologous targeting ability, enhanced stability, and 77.8% drug loading. Both in vitro and in vivo studies have indicated that biomimetic NPs provide efficient triple-modal guidance for NIR-II fluorescence, photoacoustic, and photothermal imaging and complete tumor elimination via photothermal therapy (PTT). Additionally, theranostics-based treatments with good biosecurity are demonstrated. This study contributes a new strategy for the design of high-drug-loading NIR-II theranostics and further promotes the clinical translation of theranostic agents.

NIR-II Image-Guided Wound Healing in Hypoxic Diabetic Foot Ulcers: The Potential of Ergothioneine-Luteolin-Chitin Hydrogels.

Hypoxic diabetic foot ulcers (HDFUs) pose a challenging chronic condition characterized by oxidative stress damage, bacterial infection, and persistent inflammation. This study introduces a novel therapeutic approach combining ergothioneine (EGT), luteolin (LUT), and quaternized chitosan oxidized dextran (QCOD) to address these challenges and facilitate wound healing in hypoxic DFUs. In vitro, assessments have validated the biosafety, antioxidant, and antimicrobial properties of the ergothioneine-luteolin-chitin (QCOD@EGT-LUT) hydrogel. Furthermore, near-infrared II (NIR-II) fluorescence image-guided the application of QCOD@EGT-LUT hydrogel in simulated HDFUs. Mechanistically, QCOD@EGT-LUT hydrogel modulates the diabetic wound microenvironment by reducing reactive oxygen species (ROS). In vivo studies demonstrated increased expression of angiogenic factors mannose receptor (CD206)and latelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), coupled with decreased inflammatory factors tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6), thereby promoting diabetic wound healing through up-regulation of transforming growth factor β-1 (TGF-β1).

Spacer Twisting Strategy to Realize Ultrabright Near-Infrared II Polymer Nanoparticles for Fluorescence Imaging-Guided Tumor Phototheranostics.

Conjugated polymers are becoming popular near-infrared II (NIR-II) phototheranostic agents (PTAs) due to their numerous advantages, such as high photostability, large molar extinction coefficients, and excellent photothermal properties. However, the strong π-π interactions between the chains of the conjugated polymers resulted in their generally low NIR-II emission quantum yields (QY). Therefore, the synthesis of conjugated polymers with high QY is an interesting but challenging task. Herein, we proposed a spacer twisting strategy to realize ultrabright NIR-II polymer nanoparticles for fluorescence imaging-guided tumor phototheranostics. Theoretical calculations indicated that the polymer PY-IT has the largest dihedral angle between the largely π-conjugated skeleton and the spacer, which can effectively inhibit intermolecular π-π stacking, resulting in an improved QY as high as 16.5% in nanoparticles. In addition, PY-IT NPs can effectively perform NIR-II imaging and photothermal treatment of tumors. The work presents some valuable guides for achieving ultrabright NIR-II polymeric PTAs with high QY.

NIR-II light based combinatorial management of hypertrophic scar by inducing autophagy in fibroblasts

The hypertrophic scar (HS) is a prevalent cutaneous fibrotic disorder that impacts both the aesthetic and functional aspects of the skin, there is an urgent need for a highly safe and effective approach to address the challenge of HS with thick and deep types. Inspired by the superior deep tissue penetrative ability of near-infrared-II (NIR-II) light and potential mitochondria ROS inducing effect of Chinese medicine lycorine (LYC), we fabricated a Cu2Se@LYC (CL) composite by encapsulating LYC on polyvinyl pyrrolidone (PVP) modified Cu2Se nanoparticles. After NIR-II irradiation, CL could induce the generation of reactive oxygen species (ROS) and mitochondrial damage in hypertrophic scar fibroblasts (HSFs). The subsequent release of cytochrome C (cyt-c) from mitochondria into the cytoplasm and upregulation of beclin1 leads to the activation of endogenous apoptosis and autophagy-mediated cell death. The CL + NIR-II treatment exhibited a pronounced anti-scarring effect in both in vitro and in vivo rabbit ear scar models, leading to a significant reduction in the fibrotic markers including Collagen I/III and α-smooth muscle actin (α-SMA). This study comprehensively investigated the crucial role of HSFs’ autophagy in scar management and proposed a safe and effective therapy based on NIR-II laser for clinical application.

Phototheranostic LPP-QDs-IR-820 Nanocomposites for Specific NIR-II Imaging of Lymphatic and Photothermal Therapy of Cervical Tumors.

Precise theranostics of tumors is intricately linked to the early detection and monitoring of lymph nodes (LN) and metastases, making the targeted localization of LNs essential for tumor identification. However, designing LN-targeting probes remains a significant challenge due to issues such as lymphatic uptake, biocompatibility, and fluorescence stability. To address these challenges, near-infrared II (NIR-II) fluorescence probes are developed through meticulous analysis of LN physiological structure and passive targeting strategy for LN detection and tumor therapy. An LPP-QDs-IR-820 nanocomposite (NCs) is engineered, comprising the IR-820 molecules and ultrabright PbS@CdS quantum dots (QDs), which are encapsulated within a liposome-SH-mPEG2000 polymer matrix. These NCs demonstrates remarkable lymphatic enrichment, facilitating real-time tracking of LN via electrostatic repulsion and extracellular matrix effects. Importantly, the NCs exhibit negligible in vivo toxicity and high biocompatibility. The intense NIR-II fluorescence emissions of IR-820 and PbS@CdS QDs confer upon the NCs a high NIR-II fluorescence quantum yield (6%). The cervical tumors and their deep microvessels are clearly observed via NIR-II fluorescence imaging. Moreover, the photothermal properties of IR-820 enable the NCs to achieve a photothermal conversion efficiency of 36.56%, leading to effective photothermal therapy in cervical tumor mice.

A NIR-II Organic Dendrimer with Superb Photothermal Performance Based on Electron-Donor Iteration for Photothermal Immunotherapy.

Organic photothermal materials have attracted extensive attention due to their designable molecular structure, tunable excited-state properties, and excellent biocompatibility, however, the development of near-infrared II (NIR-II) absorbingorganic photothermal materials with high photothermal conversion efficiency (PTCE) and molar extinction coefficient (ɛ) remains challenging. Herein, a novel "electron-donor iteration" strategy is proposed to construct organic photothermal dendrimers (CR-DPA-T, CR-(DPA)2-T and CR-(DPA)3-T) with donor-π-acceptor-π-donor (D-π-A-π-D) features and diradical characteristics. Owing to the enhanced D-A effect and intramolecular motions, their absorption and photothermal capacity increase as the generation grows. Surprisingly, an excellent photothermal performance (ɛ1064 ×PTCE1064) with a superb value of 2.85×104 in the NIR-II region is achieved for CR-(DPA)3-T nanoparticles (CR-(DPA)3-T NPs) compared to most reported counterparts. Besides, CR-(DPA)3-T NPs exhibit superior antitumor efficacy by the synergistic effect of photothermal therapy (PTT)and immunotherapy, efficiently inhibiting the growth of both primary and distant tumors. To the best knowledge, organic photothermal dendrimer is for the first time reported, and a universal donor engineering strategy is offered to develop NIR-II-absorbing organic photothermal materials for photothermal immunotherapy.

Symmetrically Fluorinated D-π-A Structured Cyanine Dye for Highly Efficient NIR-II Imaging-Guided Cancer Phototheranostics.

Near-infrared-II (NIR-II) fluorescence imaging-guided photothermal therapy (PTT) represents a cutting-edge approach for precise tumor diagnosis and treatment, providing real-time therapeutic efficacy evaluation. However, a significant challenge lies in the creation of phototheranostic agents that provide robust imaging and efficient photothermal conversion. To address this, a donor-π-acceptor (D-π-A) structure heptamethine cyanine derivative, IR1116, that confers a strong intramolecular charge transfer effect is developed. To enhance its applicability, IR1116 is formulated with DSPE-PEG to create a water-dispersible NIR-II phototheranostic nanoheater, NPIR1116. This nanoheater benefits from the incorporation of an electron-withdrawing group, leading to reduced photooxidation activity and significantly improved photostability. NPIR1116 exhibits strong NIR-II absorption and fluorescence, peaking at 1004 and 1116nm, respectively, as well as a photothermal conversion efficiency of 79% under 1064nm lasers. In vitro and in vivo studies showed the efficacy of NPIR1116 in tumor imaging via NIR-II fluorescence and its ability to effectively induce tumor cell apoptosis under 1064nm laser irradiation. These findings underscore the potential of NPIR1116 in NIR-II fluorescence imaging-guided PTT for tumor treatment, paving the way for further advancements in NIR-II dye development and bioimaging technologies.

Neutrophil elastase-activated carbon dots for non-invasive early diagnosis of inflammatory bowel disease by near-infrared-II fluorescence imaging

Most near-infrared-II (NIR-II) fluorescent probes produce an “always-on” output with poor signal specificity for biomarkers. Neutrophil elastase (NE) is a critical factor in chronic inflammation or in the acute response to infection and injury, and NE activatable NIR-II fluorescent probes can aid in the early clinical diagnosis of inflammatory bowel disease (IBD). In this paper, we synthesized OPDG-PFA@PEI carbon dots (CDs) through a two-step reaction of solvothermal/surface covalent bond modification, which can “turn on” specific NIR-II fluorescence signals related to the level of NE produced by neutrophils and target sites of inflammation effectively, thus realizing the monitoring of in-situ NE in cells and in vivo. OPDG-PFA@PEI CDs fluorescent nanoprobe show high-performance real-time non-invasive NIR-II fluorescence imaging for early diagnostic evaluation of IBD in mouse models of DSS-induced IBD, providing a promising approach for the development of clinical non-invasive and more convenient early diagnosis of IBD.