Plant-Derived Chinese Herbal Hydrogel Microneedle Patches for Wound Healing.

Several natural Chinese herbal medicines have demonstrated considerable potential in facilitating wound healing, while the primary concern remains centered around optimizing formulation and structure to maximize their efficacy. To address this, a natural microneedles drug delivery system is proposed that harnesses gelatinized starch and key Chinese herbal ingredients-aloe vera and berberine. After gelatinized and aged in a well-designed mold, the starch-based microneedles are fabricated with suitable mechanical strength to load components. The resulting Chinese herbal hydrogel microneedles, enriched with integrated berberine and aloe, exhibit antibacterial, anti-inflammatory, and fibroblast growth-promoting properties, thereby facilitating wound healing in the whole process. In vivo experimental results underscore the notable achievements of the microneedles in early-stage antibacterial effects and subsequent tissue reconstruction, contributing significantly to the overall wound healing process. These results emphasize the advantageous combination of traditional Chinese medicine with microneedles, presenting a novel strategy for wound repair and opening new avenues for the application of traditional Chinese medicine.

Cuttlefish-Inspired Photo-Responsive Antibacterial Microparticles with Natural Melanin Nanoparticles Spray.

Topical antibiotics can be utilized to treat periodontitis, while their delivery stratagems with controlled release and long-lasting bactericidal inhibition are yet challenging. Herein, inspired by the defensive behavior of cuttlefish expelling ink, this work develops innovative thermal-responsive melanin-integrated porous microparticles (MPs) through microfluidic synthesis for periodontitis treatment. These MPs are composed of melanin nanoparticles (NPs), poly(N-isopropylacrylamide) (PNIPAM), and agarose. Benefiting from the excellent biocompatibility and large surface area ratio of MPs, they can deliver abundant melanin NPs. Under near-infrared irradiation, the melanin NPs can convert photo energy into thermal energy. This leads to agarose melting and subsequent shrinkage of the microspheres induced by pNIPAM, thereby facilitating the release of melanin NPs. In addition, the released melanin NPs can serve as a highly effective photothermal agent, displaying potent antibacterial activity against porphyromonas gingivalis and possessing natural anti-inflammatory properties. These unique characteristics are further demonstrated through in vivo experiments, showing the antibacterial effects in the treatment of infected wounds and periodontitis. Therefore, the catfish-inspired photo-responsive antibacterial MPs with controlled-release drug delivery hold tremendous potential in clinical antibacterial applications.

Multifunctional photodynamic/photothermal nano-agents for the treatment of oral leukoplakia.

Oral leukoplakia (OLK) has gained extensive attention because of the potential risk for malignant transformation. Photosensitizers (PSs) played an indispensable role in the photodynamic therapy (PDT) of OLK, but the poor light sensitivity greatly hampered its clinical application. Herein, a novel organic photosensitive ITIC-Th nanoparticles (ITIC-Th NPs) were developed for OLK photodynamic/photothermal therapy (PTT). ITIC-Th NPs present both high photothermal conversion efficiency (~ 38%) and suitable reactive oxygen species (ROS) generation ability under 660 nm laser irradiation, making them possess excellent PDT and PTT capability. In 4-nitroquinoline 1-oxide (4NQO)-induced oral precancerous animal models, ITIC-Th NPs effectively suppress the OLK's cancerization without apparent topical or systemic toxicity in vivo. This study offers a promising therapeutic strategy for PDT and PTT in OLK treatment, and this study is the first interdisciplinary research in the field of multimodal therapy for OLK.

Thrombus-targeted nano-agents for NIR-II diagnostic fluorescence imaging-guided flap thromboembolism multi-model therapy.

In oral and maxillofacial surgery, flap repair is essential to the quality of postoperative life. Still, thrombosis is fatal for the survival of the flaps. Besides, some postoperative thrombotic diseases, such as pulmonary embolism, also intimidate patients' life. The traditional diagnostic methods are still limited by a large amount of hardware and suffer from inconvenience, delay, and subjectivity. Moreover, the treatments mainly rely upon thrombolytics, such as urokinase (UK) plasminogen activator, which may cause bleeding risk, especially intracerebral hemorrhage. Herein, a kind of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing a first near-infrared window (NIR-I) phototheranostic agent Y8 and urokinase plasminogen activator (UK) as the core, and modified with the fibrin-targeting peptide Gly-Pro-Arg-Pro-Pro (GPRPP) were developed for the flap and postoperative thromboembolism treatment (named GPRPP-Y8U@P). The conjugated molecule Y8 endows GPRPP-Y8U@P with the capacity of NIR-II imaging and excellent photothermal/photodynamic therapeutic effects. In vivo experiments demonstrated that GPRPP-Y8U@P could quickly locate thrombus by NIR-II fluorescence imaging, and semi-quantitative analysis of the embolized blood vessels' paraffin section verified its thrombolytic efficiency. Additionally, the urokinase trapped in the NPs would not result in nonspecific bleeding, tremendously improving physical security and curative effects with minimizing side effects. Overall, the advantages of GPRPP-Y8U@P, such as precise localization of the thrombus, thrombus ablation in the site, and mild side effects, demonstrated the attractiveness of this approach for effective clinical monitoring of thrombus therapy.

Optical nano-agents in the second near-infrared window for biomedical applications.

The optical technology presents non-invasive, non-destructive, and non-ionizing features and has the ability to display various chemical components in tissues to provide useful information for various biomedical applications. Regarding selection of light wavelengths, second near-infrared (NIR-II, 900-1700 nm) light is a much better choice compared to both visible (380-780 nm) and traditional near-infrared (780-900 nm) light, because of its advantages including deeper penetration into biological tissues, less tissue scattering or absorption, and decreased interference by fluorescent proteins. Thus, using optical nano-agents that absorb or emit light in the NIR-II window can achieve deeper tissue optical imaging with higher signal-to-background ratios and better spatial resolution for diagnosis. What's more, some of these nano-agents can be further applied for imaging guided surgical removal, real-time monitoring of drug delivery, labeling lymphatic metastasis, biosensing, and imaging guided phototherapy. In this review, we attempt to summarize the recent advances of various NIR-II nano-agents (including single-walled carbon nanotubes, quantum dots, rare-earth doped nanoparticles, other inorganic nanomaterials, small organic molecule-based nanoparticles, and semiconducting polymer nanoparticles) in both bioimaging and therapeutic applications, and discuss the challenges and perspectives of these nano-agents for clinical practice in the near future.

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage.

Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague-Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Breadmaking-Inspired Antioxidant Porous Yeast Microcarriers for Stem Cell Delivery in Diabetic Wound Treatment.

Stem cell-based therapies have exhibited significant promise in the treatment of diabetic ulcers (DU). Nevertheless, enhancing the survival rate and functionality of transplanted stem cells poses a substantial challenge. In this study, inspired by the breadmaking process, yeast microcarriers (YMC) are devised as vehicles for stem cells to address these challenges. The fabrication of YMC involves the amalgamation of microfluidic emulsification with yeast-mediated fermentation, yielding microcarriers with outstanding biocompatibility, high porosity, and antioxidant activity. Adipose-derived stem cells (ADSCs) seeded onto YMC display remarkable cell viability and retain their cellular functions effectively. Additionally, YMC boast a rich glutathione content and exhibit remarkable ROS scavenging ability, thus shielding the ADSCs from oxidative stress. In vivo experiments further substantiate that ADSC@YMC implementation significantly lowered ROS levels in diabetic wounds, resulting in enhanced stem cell retention and improved angiogenesis, collagen deposition, and tissue regeneration. These results highlight the potential of ADSC@YMC as a promising platform for delivering stem cell in the treatment of diabetic wounds.

Bee Sting-Inspired Inflammation-Responsive Microneedles for Periodontal Disease Treatment.

Periodontal lesions are common and frustrating diseases that impact life quality. Efforts in this aspect aim at developing local drug delivery systems with better efficacy and less toxicity. Herein, inspired by the sting separation behavior of bees, we conduct novel reactive oxygen species (ROS)-responsive detachable microneedles (MNs) that carry antibiotic metronidazole (Met) for controllable periodontal drug delivery and periodontitis treatment. Benefiting from the needle-base separation ability, such MNs can penetrate through the healthy gingival to reach the gingival sulcus's bottom while offering minimal impact to oral function. Besides, as the drug-encapsulated cores were protected by poly (lactic-co-glycolic acid) (PLGA) shells in MNs, the surrounding normal gingival tissue is not affected by Met, resulting in excellent local biosafety. Additionally, with the ROS-responsive PLGA-thioketal-polyethylene glycol MN tips, they can be unlocked to release Met directly around the pathogen under the high ROS in the periodontitis sulcus, bringing about improved therapeutic effects. Based on these characteristics, the proposed bioinspired MNs show good therapeutic results in treating a rat model with periodontitis, implying their potential in periodontal disease.

Ultrasound-responsive matters for biomedical applications.

Ultrasound (US) is a biofavorable mechanical wave that has shown practical significance in biomedical fields. Due to the cavitation effect, sonoluminescence, sonoporation, pyrolysis, and other biophysical and chemical effects, a wide range of matters have been elucidated to be responsive to the stimulus of US. This review addresses and discusses current developments in US-responsive matters, including US-breakable intermolecular conjugations, US-catalytic sonosensitizers, fluorocarbon compounds, microbubbles, and US-propelled micro- and nanorobots. Meanwhile, the interactions between US and advanced matters create various biochemical products and enhanced mechanical effects, leading to the exploration of potential biomedical applications, from US-facilitated biosensing and diagnostic imaging to US-induced therapeutic applications and clinical translations. Finally, the current challenges are summarized and future perspectives on US-responsive matters in biomedical applications and clinical translations are proposed.

Ultrasound-Responsive Oxygen-Carrying Pollen for Enhancing Chemo-Sonodynamic Therapy of Breast Cancer.

The tumor-suppressing efficacy of either chemotherapeutics or gaseous drugs has been confirmed in treating the triple negative breast cancer (TNBC), while the efficacy of single treatment is usually dissatisfactory. Herein, a novel ultrasound responsive natural pollen delivery system is presented to simultaneously load chemotherapeutics and gaseous drugs for synergistic treatment of TNBC. The hollow structure of pollen grains carries oxygen-enriched perfluorocarbon (PFC), and the porous spinous process structure adsorbs the chemotherapeutic drug doxorubicin (DOX) (PO/D-PGs). Ultrasound can trigger the oxygen release from PFC and excite DOX, which is not only a chemotherapeutic but also a sonosensitizer, to realize chemo-sonodynamic therapy. The PO/D-PGs are demonstrated to effectively enhance oxygen concentration and increase the production of reactive oxygen species in the presence of low-intensity ultrasound, synergistically enhancing the tumor killing ability. Thus, the synergistic therapy based on ultrasound-facilitated PO/D-PGs significantly enhances the antitumor effect in the mouse TNBC model. It is believed that the proposed natural pollen cross-state microcarrier can be used as an effective strategy to enhance chemo-sonodynamic therapy for TNBC.

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.

Rhythm Mild-Temperature Photothermal Therapy Enhancing Immunogenic Cell Death Response in Oral Squamous Cell Carcinoma.

The low antitumor efficiency and unexpected thermo-tolerance activation of mild-temperature photothermal therapy (mPTT) severely impede the therapeutic efficacy, thereby the implementation of reasonable mPTT procedure to improve antitumor efficiency is of great significance for clinical transformation. Herein, a rhythm mPTT with organic photothermal nanoparticles (PBDB-T NPs) is demonstrated, synergistically increasing tumor elimination and intense immunogenic cancer cell death (ICD) to elicit tumor-specific immune responses for tumor treatment. Specifically, PBDB-T NPs are characterized by favorable biocompatibility, excellent and controllable photothermal properties, exhibit the properties of noninvasive diagnostic imaging, and effective mPTT against oral squamous cell carcinoma (OSCC). Encouragingly, a temperature-dependent release of damage-associated molecular patterns (DAMPs) is discovered during the mPTT-induced ICD. Meanwhile, orchestrated rhythm mPTT referring to radiotherapy procedure amplifies and balances antitumor efficiency and abundant DAMPs generation to gain optimal immune activation within clinical-recommended hyperthermia temperature compared with conventional PTT. The in vitro and in vivo results show that the rhythm mPTT unites the killing effect and ICD induction, generating strong mPTT efficacy and active tumor-specific adaptive immune responses. The study offers a promising strategy and a new opportunity for the clinical application of mPTT.

Cholesterol Metabolism Modulation Nanoplatform Improves Photo-Immunotherapeutic Effect in Oral Squamous Cell Carcinoma.

Impressive results in cancer treatment have been obtained through immunotherapy. However, abnormally high cholesterol metabolism in the tumor microenvironment (TME) leads to poor immunogenicity or even immunosuppression, which dramatically reduces the clinical response of patients with oral squamous cell carcinoma (OSCC) to immunotherapy. In this study, a cholesterol-modulating nanoplatform (PYT NP) is developed to restore the normal immune microenvironment, significantly inhibiting SQLE (an essential gene for cholesterol biosynthesis in tumor cells) by releasing terbinafine, thereby reducing cholesterol in the TME and suppressing tumor cell proliferation. In addition, the nanoplatform is equipped with a second near-infrared (NIR-II) photosensitizer, Y8, which triggers immunogenic cell death of tumor cells, thereby promoting intra-tumor infiltration and immune activation via the production of damage-associated molecular patterns for photoimmunotherapy. PYT NPs show great promise in stimulating strong cholesterol-modulating anticancer immunity combined with photoimmunotherapy, opening up a new avenue for sensitized OSCC immunotherapy.

Achieving Extreme Pressure Resistance to Liquids on a Super-Omniphobic Surface with Armored Reentrants.

Static repellency and pressure resistance to liquids are essential for high-performance super-omniphobic surfaces. However, these two merits appear mutually exclusive in conventional designs because of their conflicting structural demands: Static liquid repellency necessitates minimal solid-liquid contact, which in turn inevitably undercuts the surface's ability to resist liquid invasion exerted by the elevated pressure. Here, inspired by the Springtail, these two merits can be simultaneously realized by structuring surfaces at two size scales, with a micrometric reentrant structure providing static liquid repellency and a nanometric reentrant structure providing pressure resistance, which dexterously avoids the dilemma of their structural conflicts. The nanometric reentrants are densely packed on the micrometric ones, serving as "armor" that prevents liquids invasion by generating multilevel energy barriers, thus naming the surface as the armored reentrants (AR) surface. The AR surface could repel liquids with very low surface tensions, such as silicone oil (21 mN m-1 ), and simultaneously resist great pressure from the liquids, exemplified by enduring the impact of low-surface-tension liquids under a high weber number (>400), the highest-pressure resistance ever reported. With its scalable fabrication and enhanced performance, our design could extend the application scope of liquid-repellent surfaces toward ultimate industrial settings.

Abalone-Inspired Adhesive and Photo-Responsive Microparticle Delivery Systems for Periodontal Drug Therapy.

Antibiotics provide promising strategies for treating periodontitis, while their delivery and controllable release with desired oral retention remain challenging. Here, inspired by the unique suction-cup structures of abalones, a novel adhesive and photo-responsive microparticle (MP) delivery system is developed to treat periodontitis through microfluidic electrospray technology. Such MPs are generated by quickly ionic cross-linking of sodium alginate together with photo-curing of poly(ethylene glycol) diacrylate of the distorted microfluidic droplets during their high-speed dropping into calcium chloride solution. Attributing to their unique concave structures, the abalone-inspired MPs exhibit desired underwater adhesion ability and stability under running water. In addition, due to the loading of antibiotics minocycline hydrochloride and near-infrared (NIR)-responsive black phosphorus during their fabrication, the resultant MPs can not only eradicate bacteria directly, but also realize a controllable and effective drug release upon NIR irradiation. Based on these features, it is demonstrated from in vivo periodontitis that the abalone-inspired MPs are firmly adhesive and can controlled-release drugs on the tooth, and thus have outstanding antibacterial efficacy against Porphyromonas gingivalis. These results indicate the particular values of the abalone-inspired MPs for oral-related disease treatment.

HSP90AB1 Promotes the Proliferation, Migration, and Glycolysis of Head and Neck Squamous Cell Carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Heat shock protein 90 alpha family class B member 1 (HSP90AB1) is highly expressed in a variety of cancers and is associated with poor prognosis, however, its role in HNSCC is still poorly understood. This study aimed to explore the function HSP90AB1 played in HNSCC progression. Methods: The expression level of HSP90AB1 in HNSCC was analyzed by bioinformatics analysis and western blotting, and its relationship with clinicopathological parameters was analyzed by bioinformatics analysis and immunohistochemistry. Three stable HSP90AB1 knockdown HNSCC cell lines were constructed by lentiviral transfection. The effect of HSP90AB1 knockdown on the proliferation and migration of HNSCC cells was tested by CCK-8 assay, EdU incorporation assay, colony formation assay, nude mouse xenograft models, transwell migration assay, wound healing assay, and western blotting. The effect of HSP90AB1 knockdown on glycolysis in HNSCC cells was assessed by quantitative real-time PCR and related assay kits. Finally, the levels of Akt and phospho-Akt (Ser473) proteins after HSP90AB1 knockdown were detected by western blotting. Results: HSP90AB1 was highly expressed in HNSCC and associated with T grade, lymph node metastasis, and prognosis. Knockdown of HSP90AB1 inhibited the proliferation, migration, and glycolysis of HNSCC, and reduced the level of phospho-Akt. Conclusion: HSP90AB1 functions as an oncogene in HNSCC, and has the potential to become a prognostic factor and therapeutic target.

Organic Near-Infrared-II Nanophotosensitizer for Safe Cancer Phototheranostics and Improving Immune Microenvironment against Metastatic Tumor.

Current tumor immunotherapy has excellent application prospects compared with traditional radiotherapy and chemotherapy, but there are still limitations, such as considerable side effects. This problem can be partially solved by treating the local tumor to induce antitumor immunity. In our study, a novel organic photosensitizer Y8 was used to synthesize nanoparticles (Y8 NPs) via a simple nanoprecipitation method. Further investigation indicated the practical photodynamic and photothermal effects of Y8 NPs with 808 nm laser irradiation. Because of its long-wavelength absorption, Y8 NPs also have excellent imaging effects near-infrared-II region. In metastatic tumor-bearing murine models, Y8 NPs can effectively induce phototherapy, suppressing the growth of both primary and metastatic tumors without apparent systemic toxicity through local photodynamic and photothermal therapy synergistic enhancement of antitumor immunity. This study offers a promising therapeutic strategy for synergetic phototherapy and immunotherapy in tumor treatment.

Novel semiconducting nano-agents incorporating tirapazamine for imaging guided synergistic cancer hypoxia activated photo-chemotherapy.

For cancer treatment, the traditional monotherapy has the problems of low drug utilization rate, poor efficacy and easy recurrence of the cancer. Herein, nanoparticles (NPs) based on a novel semiconducting molecule (ITTC) are developed with excellent photostability, high photothermal conversion efficiency and good 1O2 generation ability. The chemotherapy of the hypoxia-activated prodrug tirapazamine (TPZ) was improved accordingly after oxygen consumption by the photodynamic therapy of ITTC NPs. Additionally, the metabolic process of ITTC NPs in vivo could be monitored in real time for fluorescence imaging guided phototherapy, which presented great passive targeting ability to the tumor site. Remarkably, both in vitro and in vivo experiments demonstrated that the combination of ITTC NPs and TPZ presented excellent synergistic tumor ablation through photothermal therapy, photodynamic therapy and hypoxia-activated chemotherapy with great potential for clinical applications in the future.

Fused-Ring Small-Molecule-Based Bathochromic Nano-agents for Tumor NIR-II Fluorescence Imaging-Guided Photothermal/Photodynamic Therapy.

Optical imaging in the second near-infrared (NIR-II) windows reduces much more autofluorescence and photon scattering from biological tissues and allows further tissue penetration depth and superior spatial resolution in living bodies. Herein, a fused-ring 2,2'-((2Z,2'Z)-((12,13-bis(2-ethylhexyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2,″3″:4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (TPBT) molecule was explored as a multifunctional tumor theranostic reagent for photothermal/photodynamic therapy guided by NIR-II imaging. The TPBT molecule has an electron-deficient core with a ladder-type multi-fused ring and shows a narrow band gap that can enhance the near-infrared absorption. The J-aggregative TPBT NPs were formed by nanoprecipitation with great bathochromic shift in absorption and emission spectra, which endows them with ideal fluorescence imaging ability in the NIR-II region. Moreover, TPBT NPs present both higher photothermal conversion efficiency (∼36.5%) and effective ROS generation ability, making them excellent candidate for cancer photothermal/photodynamic therapy. Moreover, the biocompatible TPBT NPs can effectively passively target tumor sites due to their enhanced permeability and retention effect for more precision treatment. Thus, TPBT NPs as a multifunctional phototheranostic agent in the NIR-II region present promising potential in clinical cancer NIR-II imaging-guided phototherapy.

Novel NIR-II semiconducting molecule incorporating sorafenib for imaging guided synergetic cancer phototherapy and anti-angiogenic therapy.

Tumor tissues are not only independent of cancer cells, but also tumor blood vessels. Thus, targeting the tumor blood vessels is as important as targeting the tumor for cancer treatment. Herein, an organic semiconducting molecule named T8IC is developed for the potential phototeranostics in the second near-infrared window (NIR-II, 1000-1700 nm). The T8IC molecule with an electronic-rich core and electron-deficient side edge shows a typical semiconducting structure, which makes the bandgap narrow. With the addition of anti-angiogenic agent sorafenib into T8IC, TS nanoparticles (NPs) were formed by nanoprecipitation with synergetic anti-angiogenic and phototheranostic effects. Compared to the molecular state, the J-aggregative TS NPs were formed with great bathochromic-shifts in both the absorption spectrum (maximum increased from 755 nm to 826 nm) and the emission spectrum (maximum increased from 840 nm to 1030 nm), which endow them with the ideal deep tumor NIR-II fluorescence imaging ability. Besides, TS NPs present both high photothermal conversion efficiency (∼32.47%) and good ROS generation ability, making them possess excellent cancer phototherapy capability. Guided by NIR-II fluorescence imaging, the tumor blood vessels can be cut off via sorafenib and cancer cells can be killed via T8IC simultaneously, making TS NPs show promising potential for the synergistic therapeutic effect in clinical applications.