Near-infrared II Research Articles

Hematoxylin Nuclear Stain Reports Oxidative Stress via Near-Infrared Emission.

Hematoxylin & eosin (H&E) is the gold standard histological stain used for medical diagnosis and has been used for over a century. Herein, we examined the near-infrared II (NIR-II) fluorescence of this stain. We observed significant NIR-II emission from the hematoxylin component of the H&E stain. We found that the emission intensity, using the common aluminum(III) hematoxylin mordant, could be modulated by the availability of endogenous iron(III), and this emission intensity increased at higher oxidative stress. Our mechanistic investigations found that hematoxylin emission reported the nuclear translocation of the iron via the protein ferritin. In human tumor tissue samples, oxidative stress biomarkers correlated with hematoxylin NIR-II emission intensity. Emission response of the stain was also observed in human Alzheimer's disease brain tissue regions affected by disease progression, suggesting that ferritin nuclear translocation is preserved in these regions as an oxidative stress response. These findings indicate that NIR-II emission from the H&E stain provides a new source of redox information in tissues with implications for biomedical research and clinical practice.

Near-infrared-II balanced ambipolar phototransistors realized by the optimized planar-heterojunction channel layer and charge-transfer-complex photosensitive layer

Ambipolar organic phototransistors (OPTs) operating in the near-infrared II (NIR-II) were successfully fabricated by using an organic planar-heterojunction channel layer and an organic–inorganic charge-transfer-complex (CTC) photosensitive layer. After optimizations of the ratio of vanadium pentoxide in CTC hybrid system and the substrate temperature of the deposited channel layer, the devices shows the most balanced output characteristics in the dark and under 1310 nm light illumination. These OPTs yielded significantly enhanced currents upon infrared light illumination with the photoresponsivities as high as 0.115 A/W for the n-channel, and 2.600 A/W for the p-channel, respectively. By analyzing the energy band of the heterojunction structure, the operating mechanisms of the balanced ambipolar NIR-II OPTs were derived. This work will be helpful to design the ambipolar infrared phototransistor and brings forward design thought of realization of optical complementary MOS logic circuits in the future.

Single Atom-Engineered NIR-II Gold Clusters with Ultrahigh Brightness and Stability for Acute Kidney Injury.

Near-infrared-II (NIR-II) imaging has shown great potential for monitoring the pathological progression and deep tissue imaging but is limited to present unmet NIR-II agent. Present fluorophores show a promising prospect for NIR-II imaging, but brightness and photostability are still highly challenging during real-time monitoring. In this work, atom-engineered NIR-II Au24 Cd1 clusters with ultrahigh brightness, stability, and photostability are developed via single atomic Cd doping. Single atom Cd substitutions contribute to Cd 4d state in HOMO and redistribution of energy level near the gap, exhibiting 56-fold fluorescence enhancement of Au24 Cd1 clusters. Meanwhile, single atomic Cd reinforces CdAu bond energy, formation energy, and stabilized cluster structure, leading to persistent stability for up to 1month without decay, as well as excellent photostability of 1h without photobleaching, much longer than clinically approved indocyanine green (<5min). In vivo imaging shows gold clusters can monitor acute kidney injury (AKI) even after 72h of injury, enabling evaluating progression at a very long window. Meanwhile, the bioactive gold clusters can alleviate AKI-induced oxidative stress damage and acute neuroinflammation. Single atom-engineered gold clusters exhibit molecular tracking and diagnostic prospect in kidney-related diseases.

NIR-II Light-Activated Gold Nanorods for Synergistic Thermodynamic and Photothermal Therapy of Tumor.

There are tricky challenges in tumor therapy due to the hypoxic tumor microenvironment, inevitably inhibiting the treatment efficacy of the traditional photodynamic therapy (PDT), radiation therapy (RT), and sonodynamic therapy (SDT). Herein, to overcome tumor hypoxia limitation, we constructed a near-infrared II (NIR-II) light-triggered thermodynamic therapy (TDT) nanoplatform of Au@mSiO2-AIPH@PCM/PEG (ASAPP) by integrating the Au nanorods (Au NRs) and thermally activated alkyl free radical-releasing molecules (AIPH). Au NRs@mSiO2 was used as a photothermally responsive material and AIPH carrier, and the hot-melt phase-change material (PCM) was used as a capping agent to prevent leakage of AIPH during blood circulation. Upon NIR-II light irradiation, heat-triggered free radical release from AIPH was successfully achieved for killing cancer cells in vitro and in vivo without oxygen dependence, leading to synergistically enhanced antitumor therapy.

NIR-II light evokes DNA cross-linking for chemotherapy and immunogenic cell death.

As a DNA damaging agent, oxaliplatin (OXA) can induce immunogenic cell death (ICD) in tumors to activate the immune system. However, the DNA damage induced by OXA is limited and the ICD effect is not strong enough to enhance anti-tumor efficacy. Here, we propose a strategy to maximize the ICD effect of OXA through the mild hyperthermia generated by nanoparticles with a platinum (IV) prodrug of OXA (Pt(IV)-C16) and a near-infrared-II (NIR-II) photothermal agent IR1061 upon the irradiation of NIR-II light. The mild hyperthermia (43°C) holds advantages in two aspects: 1) increase the Pt-DNA cross-linking, leading to enhanced DNA damage and apoptosis; 2) induce stronger ICD effects for cancer immunotherapy. We demonstrated that, compared with OXA and photothermal therapy of IR1061 alone, these nanoparticles under NIR-II light irradiation can significantly improve the anti-cancer efficacy against triple-negative breast cancer 4T1 tumor. This new strategy provides an effective way to improve the therapeutic outcome of OXA. STATEMENT OF SIGNIFICANCE: OXA could induce immunogenic cell death (ICD) via stimulating immune responses by increasing tumor cell stress and death, which triggers tumor-specific immune responses to achieve immunotherapy. However, due to the insufficient Pt-DNA crosslinks, the ICD effect triggered by OXA cannot induce robust immune response. Mild hyperthermia has great potential to maximize the therapeutic outcome of oxaliplatin by increasing the Pt-DNA cross-linking to augment the immunoresponse for enhanced cancer immunotherapy.

NIR-II Imaging-Guided Mitochondrial-Targeting Organic Nanoparticles for Multimodal Synergistic Tumor Therapy.

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.

Rational design of molecular phototheranostic platform for NIR-II fluorescence imaging guided chemodynamic-photothermal combined therapy

The strategy of synergetic chemodynamic treatment (CDT) and photothermal therapy (PTT) to improve the anticancer effect has been a hot spot in the field of biomedicine. Herein, a high-performance near-infrared II (NIR-II) fluorescence imaging-guided molecular phototheranostic platform (IR-FE-Fc@DSPE-S-S-PEG) was designed via a convenient strategy. IR-FE-Fc@DSPE-S-S-PEG can serve as a PTT agent to kill cancer cells under near-infrared laser (808 nm) irradiation and a CDT agent to convert the endogenously less reactive H2O2 into the harmful •OH, simultaneously deplete the glutathione (GSH) to achieve an amplified CDT as well. Notably, PTT-induced hyperthermia can further enhance the CDT effect, achieving a synergistic PTT/CDT therapy. Due to the enhanced permeability and retention (EPR) effect and the high GSH microenvironment of the tumor, IR-FE-Fc@DSPE-S-S-PEG exhibited much higher tumor accumulation revealed by NIR-II fluorescence imaging. More importantly, IR-FE-Fc@DSPE-S-S-PEG efficiently damages tumorous tissues without inducing side effects to normal tissues under 808 nm laser irradiation. This work has proposed an alternative PTT-CDT combined therapy platform based on a rational design of disintegrable NIR-II fluorescence imaging-guided molecular for effective tumor treatment.

A Multiple-Response Cascade Nanoreactor for Starvation and Deep Catalysis Chemodynamic Assisted Near-Infrared-II Mild Photothermal Therapy.

Photothermal therapy (PTT) is hampered by the limited capacity of light penetration, non-specific thermal diffusion damage to surrounding healthy tissues, and thermoresistance originating in heat shock proteins (HSPs). Here, a triple-respondent (triphosphate, glutathione, and pH) cascade nanoreactor was designed through the glucose consumption-induced thermal sensitization strategy. The near-infrared-II (NIR-II) photothermal reagent Bi-Au was encapsulated in a glucose oxidase-based protein-polyphenol structure with the help of the zeolitic imidazolate framework-8 (ZIF-8). The composite nanosystem possesses triple-enzyme activity (glucose oxidase, peroxidase-like, and catalase-like). On one hand, the product of hydrogen peroxide from glycolysis can be converted into reactive oxygen species and oxygen to enhance the chemodynamic therapy and alleviate the state of hypoxia in tumor cells. On the other hand, glucose consumption could down-regulate the expression level of HSPs. The heat resistance ability of cells decreased under starvation and oxidative damage states, which is beneficial to reduce the temperature required for PTT and improve the efficiency of mild PTT. The cascade nanocapsule exhibited high tumor inhibition and proposed a typical synergistic strategy for starvation, chemodynamic, and NIR-II mild photothermal therapy.

A Brain-Targeting NIR-II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma.

Near-infrared-II (NIR-II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron-based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)-based NIR-II ferroptosis nanoparticles (TBTP-Au NPs) for brain-targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real-time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP-Au specifically activates the effective heme oxygenase-1-regulated ferroptosis of glioma cells to greatly extend the survival time of glioma-bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high-specificity visual anticancer drugs for clinical trials.

Titelbild: Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared‐II Imaging and Rapid Inactivation of Coronavirus (Angew. Chem. 13/2023)

The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. Receptors Enzymes Hydrogen-Bonded Organic Frameworks Metallocenes

Cover Picture: Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared‐II Imaging and Rapid Inactivation of Coronavirus (Angew. Chem. Int. Ed. 13/2023)

The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. Receptors Enzymes Hydrogen-Bonded Organic Frameworks Metallocenes

Mn-single-atom nano-multizyme enabled NIR-II photoacoustically monitored, photothermally enhanced ROS storm for combined cancer therapy

RationaleTo realize imaging-guided multi-modality cancer therapy with minimal side effects remains highly challenging.MethodsWe devised a bioinspired hollow nitrogen-doped carbon sphere anchored with individually dispersed Mn atoms (Mn/N-HCN) via oxidation polymerization with triton micelle as a soft template, followed by carbonization and annealing. Enzyme kinetic analysis and optical properties were performed to evaluate the imaging-guided photothermally synergized nanocatalytic therapy.ResultsSimultaneously mimicking several natural enzymes, namely peroxidase (POD), catalase (CAT), oxidase (OXD), and glutathione peroxidase (GPx), this nano-multizyme is able to produce highly cytotoxic hydroxyl radical (•OH) and singlet oxygen (1O2) without external energy input through parallel and series catalytic reactions and suppress the upregulated antioxidant (glutathione) in tumor. Furthermore, NIR-II absorbing Mn/N-HCN permits photothermal therapy (PTT), enhancement of CAT activity, and photoacoustic (PA) imaging to monitor the accumulation kinetics of the nanozyme and catalytic process in situ. Both in vitro and in vivo experiments demonstrate that near-infrared-II (NIR-II) PA-imaging guided, photothermally enhanced and synergized nanocatalytic therapy is efficient to induce apoptosis of cancerous cells and eradicate tumor tissue.ConclusionsThis study not only demonstrates a new method for effective cancer diagnosis and therapy but also provides new insights into designing multi-functional nanozymes.Graphical

A multifunctional nanotheranostic agent based on Lenvatinib for multimodal synergistic hepatocellular carcinoma therapy with remarkably enhanced efficacy

Lenvatinib (LT), a first-line molecular targeted therapeutic drug for hepatocellular carcinoma (HCC), has been replacing the status of Sorafenib (SF) as the clinically preferred and irreplaceable treatment for a decade. To overcome the low drug utilization and limited single efficacy of LT, ultrasmall copper sulfide nanocrystals (Cu2-xS NCs), and ultrasmall gold nanoparticle (AuNPs) were evenly wrapped into galactosamine conjugated poly(lactide-co-glycolide) (PLGA) as the drug delivery nanoparticles (CAL@PG) by nanoprecipitation. The CAL@PG NPs exhibited excellent stability under physiological conditions, whereas they released LT rapidly in the unique tumor microenvironment (TME) and high temperature, which could be provided by the near-infrared-II (NIR-II) photothermal effect of Cu2-xS NCs. Moreover, the temperature elevation, regenerated hydrogen peroxide (H2O2), and lower pH of TME could substantially boost the reaction potency of copper Fenton-like chemistry. More importantly, this combined therapy significantly improved the efficacy of LT, provided a multifunctional LT delivery system, and enriched the nanoparticle-augmented multimodal synergistic HCC therapy modality.

Iron-based and BRD4-downregulated strategy for amplified ferroptosis based on pH-sensitive/NIR-II-boosted nano-matchbox.

Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both invitro and invivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.

Glucose metabolism-inspired catalytic patches for NIR-II phototherapy of diabetic wound infection.

Medical patches hold great prospects for diabetic wound administration, while their practical effects in diabetic wound management remain mired by the complexity of wound microenvironments. Here, inspired by the biological processes of glucose metabolism, we present a catalytic microneedle patch that encapsulates near-infrared-II responsive and dual-nanozyme active Au-Cu2MoS4 nanosheets (Au-CMS NSs) for treating diabetic wound infection. Since microneedle patches have great tissue penetration ability, the Au-CMS NSs can be delivered to deep tissues and fully interact with wound environments. Benefitting from the dual nanozyme activities (glucose oxidase and catalase) and near-infrared-II photothermal performances of Au-CMS NSs, the composited catalytic patch realizes in situ glucose consumption, oxygen generation, and bacterial elimination. Notably, their repeatability of near-infrared-II responsive antibacterial capability has been proved both in vitro and in diabetic mice against methicillin-resistant Staphylococcus aureus. The catalytic patch can find wide catalytic applications in wound care and infection prevention. STATEMENT OF SIGNIFICANCE: Effective treatment of diabetic wound infection remains still challenging in the clinic owing to the complex wound microenvironments. Herein, inspired by the biological processes of glucose metabolism in lives, we propose a novel strategy to treat wound infections by modulating the diabetic wound microenvironments. A near-infrared-II (NIR-II) responsive biocatalytic microneedle patch with both glucose oxidase- and catalase-like activities capable of killing bacteria, reducing glucose level, and supplying O2 is developed. The patch not only achieves efficient antibacterial outcomes in vitro, but also is a valuable wound patch for efficient treatment of MRSA-infected wounds in diabetic mice. We anticipate that this therapeutic strategy will provide the applications in chronic inflammation and infections.

High aspect ratio plasmonic Au/Ag nanorods-mediated NIR-II photothermally enhanced nanozyme catalytic cancer therapy

Chemodynamic therapy (CDT) is based on the endogenous generation of cytotoxic hydroxyl free radicals (·OH) with high specificity and selectivity between cancer and normal cells. However, its efficacy is often limited by the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME). Therefore, the combination of CDT with other strategy to realize synergistic therapy is necessary. Herein, a versatile plasmonic Au/Ag nanorods (abbreviated as Au/Ag NRs) via anisotropic Ag overgrowth on Au nanobipyramids was rationally devised to achieve synergistic nanozyme catalytic therapy and near infrared II (NIR-II) light induced photothermal therapy (PTT) with the guidance of computed tomography (CT) imaging. As TME contains high concentrations of H+ and H2O2, Au/Ag NRs exhibited peroxidase (POD) activity to catalyze H2O2 to produce ·OH, inducing cancer cell death. Meanwhile, Au/Ag NRs showed a preeminent NIR-II photothermal effect. More importantly, the enhanced ·OH generation by in-situ heating up resulting from PTT could conversely inhibit the expression of heat shock proteins (HSPs) to abate their resistance to PTT, realizing self-augmented synergistic effect. The NIR-II photothermally enhanced nanozyme catalytic cancer therapy validly inhibited the cancer proliferation, as demonstrated via both cell and animal assays. Moreover, ideal high-contrast CT imaging was realized, owing to the X-ray attenuation capability of elemental Au. The multifunctional Au/Ag NRs hold potential in oncotherapy with imaging capability, high efficiency and low side effects.

A near-infrared IIb fluorophore for in vivo imaging and image-guided therapy of ischemic stroke

Near-infrared II (NIR-II) functional dyes can diagnose various diseases in non-invasive conditions. Dynamic visualization of ischemic stroke has the potential to expedite stroke diagnosis and facilitates timely treatment to alleviate cerebral injury in the continuum of stroke care. However, there is still a lack of effective imaging methods to visualize the infarct area of ischemic stroke. In this study, we report a near-infrared II (NIR-II, 1–1.7 μm) fluorophore HLX with the unique twisted donor-acceptor π-architecture, which exhibits strong aggregation induced emission characteristics and high fluorescence quantum yield in the NIR-II window and near-infrared IIb (NIR-IIb, 1.5–1.7 μm) region. The whole-body vascular imaging with superior clarity using HLX dots was achieved. Most importantly, HLX dots was utilized to realize NIR-IIb fluorescence imaging of ischemic stroke in animals and dynamically monitor the therapeutic efficacy of salidroside for the first time. Our studies further demonstrate the neuroprotective effects of salidroside against cerebral ischemic injury through promoting angiogenesis. Superior biocompatibility enables HLX as a potential agent in the NIR-IIb region to light up the infarcted vessels and image-guided therapy of ischemic stroke.

Inhibiting COX-2/PGE2 pathway with biodegradable NIR-Ⅱ fluorescent polymeric nanoparticles for enhanced photodynamic immunotherapy

Photodynamic therapy (PDT) capable of eliciting antitumor immune responses by inducing immunogenic cell death (ICD) holds promise for tumor suppression. However, most photosensitizers suffer from limited degradation, insufficient biocompatibility, and inabilities to generate long-wavelength fluorescence for in vivo tracking. Moreover, PDT has the inherent problem of activating the cyclooxygenase-2/prostaglandin-E2 (COX-2/PGE2) pathway and upregulating programmed cell death ligand 1 (PD-L1) expression, resulting in insufficient efficacy of photodynamic immunotherapy. Herein, we designed and synthesized a dihydroxy-containing BODIPY monomer (MonoBodipy), and then formed the biodegradable polymer (PPDT) by polycondensation reaction, which could generate reactive oxygen species (ROS) for photodynamic immunotherapy and emit near-infrared-Ⅱ (NIR-Ⅱ) fluorescence for bioimaging. Subsequently, we further utilized PPDT to encapsulate the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) to form NPPDT@CXB that could inhibit the COX-2/PGE2 pathway. NPPDT@CXB displayed great anticancer potency on osteosarcoma and ovarian cancer in vitro. Further, NPPDT@CXB could accumulate at tumor site after intravenous administration into tumor-bearing mice, generate ROS, induce ICD cascade, and trigger antitumor immune responses under an 808 nm laser irradiation. The ROS further breaks up thioketal linkages in PPDT, resulting in a rapid CXB release to inhibit the COX-2/PGE2 pathway and then downregulate the PD-L1 expression in tumor cells, which in turn leads to an effective suppression of the primary and distant tumors. This work highlighted a well biocompatible and biodegradable photosensitizer that generates ROS, emits long-wavelength fluorescence, inhibits the COX-2/PGE2 pathway, and downregulates PD-L1 expression simultaneously, exhibiting a robust photodynamic immunotherapy efficacy. This study proposed a new strategy to overcome the inherent problems of photodynamic immunotherapy and pointed out the path of future PDT development.

Precise Planar-Twisted Molecular Engineering to Construct Semiconducting Polymers with Balanced Absorption and Quantum Yield for Efficient Phototheranostics.

Semiconducting polymers (SPs) have shown great feasibility as candidates for near-infrared-II (NIR-II) fluorescence imaging-navigated photothermal therapy due to their strong light-harvesting ability and flexible tunability. However, the fluorescence signal of traditional SPs tends to quench in their aggregate states owing to the strong π-π stacking, which can lead to the radiative decay pathway shutting down. To address this issue, aggregation-induced emission effect has been used as a rational tactic to boost the aggregate-state fluorescence of NIR-II emitters. In this contribution, we developed a precise molecular engineering tactic based on the block copolymerizations that integrate planar and twisted segments into one conjugated polymer backbone, providing great flexibility in tuning the photophysical properties and photothermal conversion capacity of SPs. Two monomers featured with twisted and planar architectures, respectively, were tactfully incorporated via a ternary copolymerization approach to produce a series of new SPs. The optimal copolymer (SP2) synchronously shows desirable absorption ability and good NIR-II quantum yield on the premise of maintaining typical aggregation-induced emission characteristics, resulting in balanced NIR-II fluorescence brightness and photothermal property. Water-dispersible nanoparticles fabricated from the optimal SP2 show efficient photothermal therapeutic effects both invitro and invivo. The invivo investigation reveals the distinguished NIR-II fluorescence imaging performance of SP2 nanoparticles and their photothermal ablation toward tumor with prominent tumor accumulation ability and excellent biocompatibility.

Endoscopically guided interventional photodynamic therapy for orthotopic pancreatic ductal adenocarcinoma based on NIR-II fluorescent nanoparticles.

Rationale: Pancreatic cancer, comprising mostly pancreatic ductal adenocarcinoma (PDAC), is a highly malignant disease, typically known as a hypoxic tumor microenvironment. The application of PDT in pancreatic cancer in clinic is still hampered by several shortcomings, including the (i) deep location of pancreatic cancer, (ii) tissue damage induced by optical fibers, (iii) hypoxic microenvironment, (iv) short excitation wavelengths of traditional photosensitizers, and (v) poor delivery efficiency of photosensitizers. Methods: We designed an organic nanoparticle as photosensitizer for near-infrared II (NIR-II) fluorescent (FL) imaging that exerts a type I PDT effect on deep orthotopic pancreatic tumors under excitation by a NIR (808 nm) laser. Results: This novel photosensitizer exhibits enhanced accumulation in orthotopic pancreatic cancer in mice and could be used to effectively detect pancreatic cancer and guide subsequent laser irradiation for accurate PDT of deep pancreatic cancer. In addition, we built an endoscopic platform monitored by NIR-II FL imaging to achieve minimally invasive endoscopically guided interventional photodynamic therapy (EG-iPDT) with efficient inhibition of orthotopic pancreatic cancer, which prolonged overall survival up to 78 days compared to PBS + EG-iPDT group (*p < 0.05) in a mouse model. Conclusions: Minimally invasive EG-iPDT has promise as an intraoperative treatment for early-stage or unresectable or metastatic pancreatic cancer.