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Acta Biomaterialia · 2023 · IF 9.7

A biomimetic nanoplatform for precise reprogramming of tumor-associated macrophages and NIR-II mediated antitumor immune activation

Yang Du,Xiaohui Qian,Fenghao Lin,Bingqiang Gao,Weili Wang,Huang Yang,Weilin Wang,Yuan Ding

The therapeutic effects of photothermal therapy (PTT) are dependent on the photothermal conversion efficiency of photothermal agents (PTAs) in tumors and the subsequent activation of the antitumor immune system. However, the insufficient tumor accumulation of current PTAs and the inevitable recruitment of tumor-associated macrophages (TAMs) could further compromise the antitumor activities of PTT. To address these issues, a biomimetic photothermal nanoplatform [email protected] is developed for the targeted remodeling of TAMs, which promotes the antitumor immunity of PTT. Au nanorods with second near-infrared (NIR-II) absorptions are fabricated to serve as PTAs to induce immunogenic cell death in tumor cells. The ferric hydroxide shell coated on Au nanorods can release iron ions to repolarize M2-like TAMs into the tumoricidal M1 phenotype via P38 and STAT1-mediated signaling pathways . Moreover, the surface decoration of platelet membranes endows biomimetic nanoplatform with enhanced tumor targeting ability for precise tumor ablation and TAM regulation. Consequently, [email protected] under NIR-II laser irradiation exhibits significantly higher inhibitory effects in a poor immunogenic 4T1 tumor-bearing mouse model with a 50% complete remission rate compared to conventional PTT (0%). By simultaneously reversing the immunosuppressive tumor microenvironment, this biomimetic nanoplatform offers a promising strategy for enhancing the antitumor efficacy of PTT. Statement of significance The therapeutic effects of current photothermal therapy (PTT) are hindered by the insufficient tumor accumulation of conventional photothermal agents and the recruitment of immunosuppressive tumor-associated macrophages (TAMs) after PTT. Herein, we report a biomimetic iron-based second near-infrared (NIR-II) photothermal nanoplatform ( [email protected] ) for targeted TAMs reprogramming and NIR-II mediated anti-tumor immunity. [email protected] can actively target the tumor site with the help of surface-decorated platelet membranes. Meanwhile, iron ions would be released from [email protected] in acidic lysosomes to reprogram TAMs into tumoricidal M1-like macrophages, which promotes the antitumor responses elicited by NIR-II PTT, thereby contributing to remarkable tumor inhibitory effects, with 50% higher complete remission rate than that of conventional PTT.

CAS / MDL: 50-81-7
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Materials Today Bio · 2023 · IF 8.2

NIR responsive nanoenzymes via photothermal ablation and hypoxia reversal to potentiate the STING-dependent innate antitumor immunity

Qianzhe Li,Mengyu Yang,Xin Sun,Qinxin Wang,Beibei Yu,Aihua Gong,Miaomiao Zhang,Fengyi Du

Despite advances in combined photothermal/immunotherapy of tumor, the therapeutic effect has been impaired due to hypoxic microenvironment and inadequate immune activation. Manganese ions directly activated the stimulator of interferon genes (STING) pathway and induced innate antitumor immunity. Herein, a near infrared light (NIR)-responsive nanoenzyme (PB–Mn/OVA NE) was constructed by doping manganese into the ovalbumin (OVA)-templated Prussian blue (PB) nanoparticles. The resultant PB-Mn/OVA NEs exhibited favorable catalase activity to produce oxygen, which was conducive to alleviate the tumor hypoxic microenvironment. Under 808 ​nm NIR irradiation, the PB-Mn/OVA NEs with outstanding photothermal conversion efficiency of 30% significantly destroyed tumor cells by inducing immunogenic cell death (ICD). Impressively, the PB-Mn/OVA NEs could activate the cGAS-STING pathway to promote the maturation and the antigen cross-presentation ability of dendritic cells (DCs), which further activated cytotoxic T lymphocytes and memory T lymphocytes. Overall, this work presents a powerful nanoenzyme formula to integrate photothermal ablation and hypoxic reversal for triggering robust innate and adaptive antitumor immune response.

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International Journal of Nanomedicine · 2023 · IF 8

Surface Engineering of Metal–Organic Framework as pH-/NIR-Responsive Nanocarrier for Imaging-Guided Chemo-Photothermal Therapy

Haibin Guo,Yanqing Xia,Ke Feng,Xiaowei Qu,Cuilian Zhang,Feng Wan

Background Metal–organic frameworks (MOFs) have attracted intensive research interest in the biomedical field because of their unique properties. However, in order to realize the high loading capacity and therapeutic efficacy, it is still urgent to develop a multifunctional MOFs-based nanoplatform.Materials and Methods Herein, a pH/near-infrared (NIR) dual-responsive drug delivery system based on zeolitic imidazolate framework-8 (ZIF-8) is constructed for synergistic chemo-photothermal therapy and dual-modal magnetic resonance (MR)/photoacoustic (PA) imaging. The doxorubicin hydrochloride (DOX) is embedded into ZIF-8 through one-pot method, and the resultant ZIF-8/DOX is then successively modified with polydopamine, Mn ions and poly(ethylene glycol). The obtained ZIF-8/DMPP is systematically characterized, and both its in vitro and in vivo biological effects are evaluated in detail.Results The ZIF-8/DMPP possesses a high drug-loading content of 18.9% and displays appropriate size and morphology. The pH-dependent degradation and drug release behavior of prepared ZIF-8/DMPP are confirmed. Importantly, the results demonstrate that the photothermal effect of ZIF-8/DMPP under NIR laser irradiation can significantly accelerate its drug releasing rate, further improving the intracellular drug concentrations. Thereafter, the augmented chemotherapeutic efficiency by photothermal effect against cancer cells is verified both in vitro and in vivo. Besides, the favorable MR and PA imaging capacity of ZIF-8/DMPP is also evidenced on the tumor model.Conclusion Taken together, the surface engineering of ZIF-8-based nanocarrier in this work offers a promising strategy for the multifunctional MOFs-based drug delivery system.

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CHEMISTRY-A EUROPEAN JOURNAL · 2023 ·Vol. 29 ·期 19 ·e202203831 · IF 4.3

Ultrathin Two-Dimensional BiOCl-Bi2S3-Cu2S Ternary Heterostructures with Enhanced LSPR effect for NIR Photonic Bacterial Disinfection**

Shouning Yang,Shengkun Wang,Yaru Wang,Jian Song,Yuqin Jiang,Liang Chen,Huayan Yang

Graphical Ultrathin Two-Dimensional BiOCl-Bi 2 S 3 -Cu 2 S Ternary Heterostructures with Enhanced LSPR effect for NIR Photonic Bacterial Disinfection (Chen, Yang, et al.). : Photonic disinfection, particularly near-infrared (NIR) light triggered antibacterial, has emerged as a highly promising solution for combating pathogenic microbes due to its spatiotemporal operability, safety, and low cost of apparatus. However, it remains challenging to construct NIR-responsive antibacterial agents with high light-converting efficacy and elucidate synergistic mechanisms. In this work, ultrathin two-dimensional (2D) BiOCl-Bi 2 S 3 -Cu 2 S ternary heterostructures that can efficiently kill drug-resistant bacteria were synthesized by doping 0D Bi 2 S 3 and Cu 2 S nanoparticles in the 2D BiOCl nanosheets via a facile one-pot hydrothermal method. Notably, the incorporation of Cu 2 S nanoparticles bestows strong NIR light-harvesting capability to the composite nanosheets due to their localized surface plasmon resonance (LSPR). Upon NIR light illumination, the BiOCl-Bi 2 S 3 -Cu 2 S nanosheets can achieve enhanced photonic hyperthermia and reaction oxygen species (ROS) generation, serving as single light-activated bi-functional photothermal/photodynamic therapeutics. High-speed hot electrons and large local electronic fields caused by LSPR might play an important role in thermal vibrations and effective carrier separations, respectively. Benefiting from the unique ternary heterostructures, both the photothermal conversion and ROS generation efficacy of BiOCl-Bi 2 S 3 -Cu 2 S nanosheets are significantly improved compared to the binary BiOCl-Cu 2 S or BiOCl-Bi 2 S 3 nanosheets. Accordingly, the ternary composite nanosheets can effectively kill bacteria via the NIR-driven photonic disinfection mechanism. This work presents a new type of 2D composite nanosheets with ternary heterostructures for NIR photonic disinfection.

CAS / MDL: 4091-99-0
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Advanced Therapeutics · 2023 ·Vol. 6 ·期 4 ·2200350 · IF 4.6

Gold Nanocluster Encapsulated Nanorod for Tumor Microenvironment Simultaneously Activated NIR-II Photoacoustic/Photothermal Imaging and Cancer Therapy

Zhifang Li,Shulong Wang,Jingjin Zhao,Yanni Luo,Hong Liang,Shulin Zhao,Liangliang Zhang

Tumor microenvironment (TME)-responsive imaging and therapy has great potential for application towards precision diagnosis and treatment of cancer. Photoacoustic (PA) imaging with the second near-infrared window (NIR-II) and photothermal therapy are important ways to address high-resolution imaging of in vivo deep tumor tissue and high-effect therapy of cancer. A gold nanocluster (AuNCs) encapsulated nanorod (AuNRs) (AuNRs@MEA/DTGA@AuNCs, hereafter AMDAs) is prepared. The AuNRs are first modified using β-mercaptoethylamine (MEA) to form AuNRs@MEA. Dithioglycolic acid (DTGA) is coupled with AuNRs@MEA to obtain AuNRs@MEA/DTGA (AMD). Finally, AuNCs are attached to AuNRs@MEA/DTGA surface to form AMDAs. In this nanocomposite materials, the encapsulation of the AuNRs by the AuNCs obscures NIR-II PA signal of AuNRs. The high expressed glutathione in the TME react with the AMDAs via redox reaction, the detachment of the AuNCs from the AuNRs surface, and detection of the NIR-II PA signal from the AuNRs, thus enabling NIR-II PA imaging of tumor tissues. In addition, due to the high intensity light absorption of AuNRs in the NIR-II region, the release of AuNRs also enhance tumor photothermal imaging and therapy. This work establishes an accurate and efficient integrated platform for nanodiagnosis and treatment of cancer.

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Biomaterials Science · 2023 ·Vol. 11 ·期 5 ·1876-1894 · IF 6.6

Endoplasmic reticulum-targeted NIR-II phototherapy combined with inflammatory vascular suppression elicits a synergistic effect against TNBC

Guoyun Wan,Xuheng Chen,Jiayu Chen,Ruiling Gou,Haijiao Wang,Shuhao Liu,Mingyang Zhang,Hongli Chen,Dan Wang,Qiqing Zhang

Recurrence and metastasis are the main reasons for failure in the treatment of triple-negative breast cancer (TNBC). Phototherapy, one of the most well-known potent cancer treatment models is highlighted by ablating primitive tumors with immunogenic cell death (ICD) and is associated with endoplasmic reticulum (ER) stress to elicit long-lasting anti-tumor immunity. However, the provoked inflammatory response after phototherapy will stimulate angiogenesis, which provides nutrition for tumor recurrence. Here, an ER-targeted nanoplatform was constructed based on hollow mesoporous Cu2−XS (HMCu2−XS) nanoparticles to suppress recurrence and metastasis of TNBC by combining photo-ablation and microenvironment remodeling. Profiting from the metal ion coordination and large hollow space, HMCu2−XS can be easily modified with p-toluenesulfonamide for ER-targeting and quantitatively loaded celecoxib (CXB) as a vascular inhibitor, thus obtaining ER-HMCu2−XS/CXB. ER-HMCu2−XS showed great photothermal and photodynamic efficiency for ablating 4T1 tumors and inducing ICD under NIR-II laser irradiation. Compared with non-ER-targeted nanosystems, the ER-targeted nanosystem elicited stronger ICDs and recruited more immune cells. Moreover, the thermal-responsively released CXB successfully inhibited angiogenesis after photothermal therapy. The data showed that the ER-HMCu2−XS/CXB mediated the triplicate therapeutic effect of photo-ablation, immune response activation, and vascular suppression effectively, preventing the recurrence and metastasis of TNBC. In conclusion, this work provides a synergistic strategy to enhance therapeutic outcomes in TNBC.

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CARBOHYDRATE POLYMERS · 2023 · IF 11.2

Dextran 40 hybrid biomimetic bismuth-nanoflower designed for NIR II-triggered hypoxic tumor thermoradiotherapy via macrophage escape

Jing Wen,Chang Liu,Ji Liu,Lu Wang,Si Miao,Daquan Chen,Qiyue Wang,Meirong Huo,Yan Shen

At present, NIR-II-triggered photothermal biomedical applications are limited by complex synthesis reactions , mediocre photothermal conversion efficiency, and difficult degradation. Herein, we prepared biodegradable Bi flower-like nanoparticles (phospholipid-modified Bi nanoflowers , BNFs) with high photothermal conversion efficiency (∼33.52 %) in NIR-II by a simple method and then modified them with the red blood cell membrane and dextran 40 (DRBCM) to improve their in vitro stability, to escape macrophages clearance and to enhance tumor accumulation. Dextran coating onto the surface of particles as a dispersant shell stabilizes inorganic particles by maintaining the surface charges and creating steric repulsions upon compression of neighboring polymer chains. In vitro and in vivo experiments proved that combined thermoradiotherapy of DRBCM-BNFs exhibited significantly enhanced tumor inhibition efficacy than monotherapy with good biocompatibility and low toxicity due to its biodegradability . Furthermore, the mechanism studies demonstrated that DRBCM-BNFs could serve as a nano sensitizer to promote the thermoradiotherapy under NIR-II illumination and X-ray irradiation, by downregulating heat shock protein 70 (HSP70) and phosphorylated-p65 (p-p65) to reduce the thermal resistance and radioresistance of tumor cells and increasing the expression of apoptosis-related protein cleaved caspase-3. In conclusion, DRBCM-BNFs could be a promising green delivery platform for the sensitization of synergistic thermoradiotherapy.

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BIOMATERIALS · 2023 · IF 14

pH/NIR-responsive and self-healing coatings with bacteria killing, osteogenesis, and angiogenesis performances on magnesium alloy

Yanbin Zhao,Peng He,Junyan Yao,Mei Li,Bin Wang,Linyuan Han,Zhihai Huang,Chao Guo,Jing Bai,Feng Xue,Yu Cong,Weihua Cai,Paul K. Chu,Chenglin Chu

Although biodegradable polymer coatings can impede corrosion of magnesium (Mg)-based orthopedic implants , they are prone to excessive degradation and accidental scratching in practice. Bone implant-related infection and limited osteointegration are other factors that adversely impact clinical application of Mg-based biomedical implants. Herein, a self-healing polymeric coating is constructed on the Mg alloy together with incorporation of a stimuli-responsive drug delivery nanoplatform by a spin-spray layer-by-layer (SSLbL) assembly technique. The nanocontainers are based on simvastatin (SIM)-encapsulated hollow mesoporous silica nanoparticles (S@HMSs) modified with polydopamine (PDA) and polycaprolactone diacrylate (PCL-DA) bilayer . Owing to the dynamic reversible reactions, the hybrid coating shows a fast, stable, and cyclical water-enabled self-healing capacity. The antibacterial assay indicates good bacteria-killing properties under near infrared (NIR) irradiation due to synergistic effects of hyperthermia, reactive oxygens species (ROS), and SIM leaching. In vitro results demonstrate that NIR laser irradiation promotes the cytocompatibility, osteogenesis, and angiogenesis . The coating facilitates alkaline phosphatase activity and expedites extracellular matrix mineralization as well as expression of osteogenesis-related genes. This study reveals a useful strategy to develop multifunctional coatings on bioabsorbable Mg alloys for orthopedic implants .

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ACS Nano · 2023 · IF 17.1

NIR-II Responsive Nanohybrids Incorporating Thermosensitive Hydrogel as Sprayable Dressing for Multidrug-Resistant-Bacteria Infected Wound Management

Weilun Pan,Bodeng Wu,Chengtao Nie,Tingting Luo,Zhenli Song,Jie Lv,Yong Tan,Chunchen Liu,Mingzhen Zhong,Tong Liao,Zhenxun Wang,Guanghui Yi,Limin Zhang,Xiaoliu Liu,Bo Li,Jinxiang Chen,Lei Zheng

Developing an effective dressing against bacterial infection and synchronously addressing wound complications, such as bleeding, long-term inflammation, and reinfection, are highly desirable in clinical practice. In this work, a second near-infrared (NIR-II) responsive nanohybrid consisting of imipenem encapsulated liposome with gold-shell and lipopolysaccharide (LPS)-targeting aptamer, namely ILGA, is constructed for bacteria elimination. Benefiting from the delicate structure, ILGA exhibits strong affinity and a reliable photothermal/antibiotic therapeutic effect toward multidrug-resistant Pseudomonas aeruginosa (MDR-PA). Furthermore, by incorporating ILGA with a thermosensitive hydrogel poly(lactic-co-glycolic acid)–polyethylene glycol–poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA), a sprayable dressing ILGA@Gel was prepared, which enables a quick on-demand gelation (10 s) for wound hemostasis and offers excellent photothermal/antibiotic efficacy to sterilize the infected wound. Additionally, ILGA@Gel provides satisfactory wound-healing environments by reeducating wound-associated macrophages for inflammation alleviation and forming a gel layer to block exogenous bacterial reinfection. This biomimetic hydrogel reveals excellent bacteria eradication and wound recovery effectiveness, demonstrating its promising potential for managing complicated infected wounds.

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CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

NIR-AIEgens nanospheres featuring high-fidelity dynamic lipid droplet targeting, expediting ferroptosis to annihilating tumor in hypoxia

Ke Xue,Yongfei Zhao,Saidong Sun,Yuanhang Li,Jiankang Liang,Zhengjian Qi

Severe ferroptosis is a non-apoptotic iron-dependent cell death pathway, and extreme hypoxia and anomalous iron metabolism in tumors critically suppress the efficacy of ferroptosis therapy. Overcoming tumor hypoxia while facilitating ferroptosis is an extremely challenging task. Herein, the photosensitizer named BOTTQ with specific targeting of lipid droplet (LD) was synthesized by increasing the tail chain length of triphenylamine. The addition of alkoxy chains optimized the molecular structure and fostered inter-system crossing and type I reactive oxygen species (ROS) generation. Besides, BOTTQ yielded large amounts of type I ROS under light excitation oxidize efficiently polyunsaturated fatty acids in lipid monolayer of LD and contribute to the formation of ferroptosis substrate. Meanwhile, the generation of type I ROS accelerated the Fenton reaction, thus effectively boosting the occurrences of ferroptosis. Furthermore, the successful encapsulation of BOTTQ into DSPE-PEG-MAL material not only elevates the stable type of nanoparticle colloids, but the MAL moiety can deplete the functional thiols of glutathione in a mild environment, which leads to glutathione failure and facilitates ferroptosis. Thus tumor-specific ferroptosis-inducing strategy offers a universally applicable therapy with the capacity to enhance type I ROS production and effectively contain tumorigenesis.

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JOURNAL OF RARE EARTHS · 2022 · IF 4.632

Coumarin derivative dye sensitized NaYGdF4:Yb,Er nanoparticles with enhanced NIR II luminescence for bio-vascular imaging

Yaqun Ma,Zhan Wang,Yanxing Wang,Zhenghao Liu,Yukun Wang,Ruichan Lv

Lanthanide-doped biocompatible nanoparticles have promising applications in near-infrared second region imaging due to their high chemical stability, enhanced photostability and sharp emission bandwidth. However, the weak light absorption capacity limits the application of rare-earth nanoparticles (RENPs) for bioimaging. We prepared a coumarin-derived dye sensitized NaYGdF 4 :Yb,Er nanoparticle probe, in which the organic dye enhances photon absorption through the sensitization process, improving the luminescence efficiency of the rare earth particles near 1000 and 1500 nm. In addition, good water solubility and stability of the probe are imparted by coating the particles with amphiphilic polymers distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) and polyacrylic acid. This composite probe with good biocompatibility and NIR II luminescence properties can be used for vascular imaging, providing a tool for the detection of hematologic-related diseases.

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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2022 · IF 5.062

pH/NIR-responsive nanocarriers based on mesoporous polydopamine encapsulated gold nanorods for drug delivery and thermo-chemotherapy

Zehua Han,Minjie Gao,Zhihua Wang,Lichao Peng,Yanbao Zhao,Lei Sun

Gold nanorods (AuNRs) have potential application value in the field of cancer therapy. However, the poor stability, high dark toxicity, insufficient drug-carrying capacity and photothermal conversion efficiency have limited its practical applications. In this study, we encapsulated AuNRs in mesoporous polydopamine (mPDA) shells. The mPDA has exceptional adhesion, excellent biocompatibility , large specific surface area and favorable photothermal properties, making [email protected] an ideal photothermal composite and drug delivery carrier. [email protected] can generate heat under near-infrared (NIR) laser irradiation, which disrupts the intermolecular forces and hydrogen bonds between PDA shell and drug, showing a photothermal enhanced drug release. Furthermore, by using polyethyleneimine (PEI) to seal the pore channels of mPDA, the pH-/NIR-responsive nanocarrier of [email protected] @PEI was fabricated, which shows a high drug loading capacities for DOX to 121.7 mg/g. What's more, by combination of chemotherapy and photothermal therapy , the [email protected] @PEI nanocarrier exhibits significant anticancer effect in vitro . In a word, this carrier demonstrated high drug capacity, excellent photothermal conversion efficiency (55.7%) and pH/NIR stimulation-responsive delivery performance, and promising to become a nanoplatform for multifunctional cancer therapy in the future.

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