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Acta Biomaterialia · 2019 · IF 6.638

Matrix metallopeptidase 2 targeted delivery of gold nanostars decorated with IR-780 iodide for dual-modal imaging and enhanced photothermal/photodynamic therapy

Fangfang Xia,Jiaqi Niu,Yuping Hong,Chenlu Li,Wen Cao,Lirui Wang,Wenxiu Hou,Yanlei Liu,Daxiang Cui

Nanotheranostics has gained increasing interest, as it offers a great potential to realize personalized diagnostics and therapy. In this work, we report a facile approach of the fabrication of gold nanostars (GNS) attached with matrix metalloproteinases (MMP2) polypeptides (Ac-GPLGIAGQ) and IR-780 iodide through bovine serum albumin (BSA) for targeted dual-modal photoacoustic (PA)/near-infrared (NIR) fluorescence imaging and enhanced photothermal therapy (PTT)/photodynamic therapy (PDT) for lung cancer. MMP2 polypeptides served as the targeting ligand, IR-780 iodide functioned as the NIR fluorescence imaging agent as well as PTT/PDT agent, and GNS acted as the carrier of IR-780 molecules and performed PA imaging and PTT. DLS and CCK-8 assay demonstrated that the nanoprobes (GNS@BSA/I-MMP2) exhibited excellent stability and biocompatibility under physiological conditions. Subsequent in vitro studies verified that GNS@BSA/I-MMP2 nanoparticles (NPs) were effectively internalized by A549 cancer cells and exhibited remarkable antitumor efficacy. Furthermore, GNS@BSA/I-MMP2 NPs could specifically target the tumor and significantly suppress the tumor growth, and their antitumor effects were mainly through the synergistic effects of PDT and PTT based on IR-780 and GNS. These findings imply the potential of GNS@BSA/I-MMP2 NPs as a targeting PA/NIR probe in tumor diagnosis and combined therapy with a single light source. Statement of Significance We reported a convenient and facile approach to load IR-780 iodides in gold nanostars (GNS). This material could simultaneously perform near-infrared imaging/photoacoustic imaging and thermotherapy/photodynamic therapy. MMP2 coating on the surface of GNS@BSA/IR-780 promoted the prepared nanoparticles (GNS@BSA/I-MMP2) to target the tumor region. The heat generated by the synergistic effect of the GNS and IR-780 molecules resulted in the high temperature of the GNS@BSA/I-MMP2 NPs, which efficiently suppressed the growth of tumor, and the tumor volume decreased by 93% compared with that in the PBS groups with laser irradiation.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 成像科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DALTON TRANSACTIONS · 2019 ·Vol. 48 ·期 15 ·5072-5082 · IF 4.052

N-Methylation of ortho-substituted aromatic amines with methanol catalyzed by 2-arylbenzo[d]oxazole NHC–Ir(III) complexes

Shuang Huang,Xi Hong,He-Zhen Cui,Quan Zhou,Yue-Jian Lin,Xiu-Feng Hou

Seven new chelated cyclometalated Ir complexes of ABON,P, ABON,O, and ABON,C(carbene) based on a rigid and tunable 2-arylbenzo[d]oxazole backbone have been prepared for the N-methylation of amines. Among these three coordinated modes, ABON,C(carbene)-chelated iridium-based catalysts exhibited good performance in the monomethylation of aromatic amines with methanol (MeOH) as the green methylation reagent. The steric-modified synthesis of ABON,C(carbene) complexes was described. The most active ABON,C(carbene) complex with marginal steric hindrance as a catalyst was obtained from the benzoxazole ring without a substituent and methyl group of the benzimidazole ring on the N-heterocyclic carbene (NHC) ligand. A variety of amines including para- and meta-substituted aromatic amines, as well as heterocyclic amines, were formulated as suitable substrates. Importantly, this catalyst considerably promoted the yield of the N-methylation of ortho-substituted aromatic amines. Controlled kinetic experiments and deuterium-labeling reactions of these ortho-substituted amines were conducted under optimized conditions. On the basis of the experimental results, a plausible mechanism was proposed.

研究领域: 有机化学 · 催化 · 合成化学
✓ 已验证 DOI 高影响因子
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Food Bioscience · 2024 · IF 4.8

Amelioration of hypoglycemic peptide MoHpP-2 from Moringa oleifera seeds in C2C12 / IR cells and type 2 diabetes mellitus mice

Yaozhu Fan,Xuefeng Wang,Yiyan Li,Lingfei Li,Yang Tian

The hypoglycemic peptide MoHpP-2 from Moringa oleifera seeds exhibits excellent α-glucosidase inhibitory activity, but its amelioration in insulin resistant (IR) cells and type 2 diabetes mellitus (T2DM) mice is still unclear. Therefore, the present study aimed to investigate the hypoglycemic effect of MoHpP-2 on C2C12/IR cells, and gut microbiota and metabolite changes of T2DM mice using 16S rRNA high-throughput sequencing and metabolomics. MoHpP-2 within the concentration range could effectively enhance the glucose consumption levels and antioxidant capacity in C2C12/IR cells. MoHpP-2 intervention improves the blood sugar levels, liver function, and organ indices, reverses oxidative damage, and enhances the antioxidant capacity of T2DM mice. Furthermore, it increases the diversity of cecum microorganisms, decreases the ratio of Firmicutes to Bacteroides and some pathogenic bacteria , and reshapes the gut microbial composition of T2DM mice. Moreover, the metabolomic analysis results showed that MoHpP-2 intervention might promote unsaturated fatty acid biosynthesis, inhibit bile acid formation, and regulate linoleic acid metabolism and amino acid metabolism related to oxidative stress, thereby improving insulin resistance and sensitivity in T2DM mice. Overall, the experimental results provide insights into the hypoglycemic effect of MoHpP-2 in vitro and in vivo and its application in hypoglycemic functional food products.

CAS / MDL: 1115-70-4
研究领域: 药理学 · 营养学 · 微生物学 · 代谢组学
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ACS Omega · 2022 · IF 4.132

Phytochemical Screening, Quantification, FT-IR Analysis, and In Silico Characterization of Potential Bio-active Compounds Identified in HR-LC/MS Analysis of the Polyherbal Formulation from Northeast India

Prince Kumar Singh,Jagreeti Singh,Tapas Medhi,Aditya Kumar

Diabetes is a group of metabolic disorders characterized by elevated blood sugar levels, leading to many undesirable health consequences. There are many herbal formulations, traditionally used by the Northeast Indian population for disease management. These formulations require scientific validations to optimize their efficacy and increase their popularity. In this study, we attempt to scientifically validate a polyherbal formulation traditionally used for the management of diabetes through preliminary phytochemicals investigation, characterization of potential phytochemicals using Fourier transform infrared (FT-IR) spectroscopy, high-resolution liquid chromatography mass spectrometry (HR-LC/MS) analysis, and in silico characterization of physiochemical, drug-likeness, and pharmacokinetic properties of identified phytochemical compounds. Qualitative phytochemical screening of various extracts of the formulation confirmed the presence of alkaloids, phenols and tannins, flavonoids, fats, and oils. Phytochemical quantification of the various extracts showed that the highest total phenolic content is present in the ethanolic extract (35.61 ± 0.15 mg GAE/g), while the highest total flavonoid content is present in the chloroform extract (76.33 ± 2.96 mg QE/g) of the formulation. FT-IR spectroscopic analysis revealed various characteristic band values with various functional groups in the formulation extract such as amines, alcohol, fluoro compounds, phenol, alkane, alkene, and conjugated acid groups. HR-LC/MS analyses identified nearly 51 compounds including 9 small peptides and 42 potential phytochemical compounds. In silico SwissADME analysis of identified compounds revealed 25 potential compounds following Lipinski’s rule and showing drug-like characteristics, and out of them, 16 compounds exhibited good oral bioavailability, as revealed in the bioavailability radar. The overall study showed that the presented polyherbal formulation is enriched with bio-active phytochemical compounds with good pharmaceutical values.

研究领域: 药理学 · 植物化学 · 生物信息学
✓ 已验证 DOI PubMed 高影响因子
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DALTON TRANSACTIONS · 2023 · IF 4

Selectively attacking tumor cells of Ru/Ir–arene complexes based on meclofenamic acid via cyclooxygenase-2 inhibition

Yuanlei Huang,Mengdi Lv,Binglian Guo,Guojing Hu,Yong Qian,Zhi Su,Xuling Xue,Hong-Ke Liu

Breast cancer (BC) is one of the most common malignant tumors and often accompanied by inflammatory processes. Inflammation is an essential component of the tumor microenvironment, which might influence tumor proliferation and metastasis. Herein, three metal–arene complexes MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru were prepared by tethering the non-steroidal anti-inflammatory drug meclofenamic acid (MA). Among them, MA-bip-Ru and MA-bpy-Ir showed lower cytotoxicity towards cancer cells, but MA-bpy-Ru showed significantly high selectivity and cytotoxicity towards MCF-7 cells through the autophagic pathway and exhibited no toxicity against normal HLF cells, showing potential for selective treatment of tumor cells. MA-bpy-Ru could also effectively destroy the 3D multicellular tumor spheroids, demonstrating its potential for clinical application. Besides, MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru exhibited anti-inflammatory properties superior to MA, notably downregulating the expression of cyclooxygenase-2 (COX-2) and inhibiting the secretion of prostaglandin E2 in vitro. These findings demonstrated that MA-bpy-Ru was capable of intervening in inflammatory processes and showed the potential of MA-bpy-Ru to act as a selective anticancer agent, thus presenting a new mechanism of action for metal–arene complexes.

研究领域: 肿瘤学 · 药物化学 · 无机化学 · 癌症生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2018 · IF 6.383

A versatile strategy to create an active tumor-targeted chemo-photothermal therapy nanoplatform: A case of an IR-780 derivative co-assembled with camptothecin prodrug

Wenxiu He,Yue Jiang,Qian Li,Di Zhang,Zhonghao Li,Yuxia Luan

Self-assembled nanovehicles of chemotherapy drug with photothermal agent are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most of the drugs and photothermal agents have poor water solubility and poor interactions to drive the formation of self-assembled nanovehicles, which is a bottleneck of co-assembled drug/photothermal agent for cancer therapy. Here, we proposed a versatile strategy to create self-assembled chemo-photothermal therapy nanoplatform based on the chemical modification of photothermal agent and drug. The IR-780 and camptothecin (CPT) were chosen as the studied models since they are important photothermal agent and anticancer drug, both of which have such poor water solubility with strong itself molecular interactions that they cannot co-assemble together. IR-780 was modified with an active targeting ligand lactobionic acid (LA) to result in amphiphilic IR780-LA while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through a disulfide linkage to realize its assembly. Well-defined nanoparticles (NPs) could be created through the co-assembling of IR780-LA and CPT-ss-CPT. The IR780-LA/CPT-ss-CPT nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive and enhanced synergistic chemo-photothermal therapy nanoplatform against tumors. Specifically, our chemical modification strategy offers a universal way to create self-assembled chemo-photothermal therapy nanoplatform, which solves the bottleneck of co-assembled drug/photothermal agent for cancer therapy. Statement of Significance Self-assembled nanoparticles of chemotherapeutics with photothermic drugs are regarded as intriguing chemo-photothermal therapy nanoplatform. However, most drugs have too poor solubility and interactions to form into self-assembled nanoparticles. We proposed a versatile strategy to create co-assembled chemo-photothermal therapy nanoparticles based on the chemical modification of common drugs. The IR-780 was modified with an active targeting ligand LA to result in amphiphilic IR780-LA molecules, while CPT was modified into redox-sensitive prodrug CPT-ss-CPT through disulfide linkage. Well-defined IR780-LA/CPT-ss-CPT nanoparticles were created through the co-assembling of IR780-LA and CPT-ss-CPT. The nanoparticles were demonstrated to be an excellent fluorescence imaging-guided, redox-responsive, active targeting chemo-photothermal therapy nanoplatform against tumors. Our strategy offers a versatile way to construct smart chemo-photothermal therapy nanoplatform from common drugs.

研究领域: 药学 · 纳米技术 · 癌症治疗 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Biomaterials Science & Engineering · 2018 · IF 4.432

Photostability Highly Improved Nanoparticles Based on IR-780 and Negative Charged Copolymer for Enhanced Photothermal Therapy

Nannan Shao,Yanxin Qi,Hongtong Lu,Dongyun He,Bin Li,Yubin Huang

The development of near-infrared (NIR) dyes with desirable photophysical characteristics for tumor therapy is highly expected at present. In this report, IR-780 iodide was loaded by the mercaptopropionic acid grafted poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(allyl glycidyl ether) [mPEG5K-PCL10K-PAGE6 (MPA)] copolymer to form nanomicelles (IR-780@TBMPA) in aqueous solution. On account of the hydrophobic and electrostatic interaction between mPEG5K-PCL10K-PAGE6 (MPA) and IR-780, the IR-780@TBMPA micelle was structurally stable with improved solubility, light stability and biocompatibility. The encapsulation of IR-780 indicated no influence on its original physicochemical property, showing good optical and thermal characteristics. The drug-loaded micelles had appropriate microscopic size for endocytosis, displaying significant cytotoxicity to HeLa cells under NIR laser irradiation. In addition, the phototoxicity generated by photothermal and photodynamic effect of IR-780@TBMPA under 808 nm laser irradiation was also investigated by reactive oxygen species (ROS) detection and flow cytometry. Furthermore, the superior accumulation of IR-780@TBMPA in tumor tissues provided sufficient hyperthermia to kill tumor cells, indicating its potential in cancer clinical therapy.

CAS / MDL: 78-67-1
研究领域: 材料科学 · 纳米技术 · 癌症治疗 · 药学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Catalysis · 2024 · IF 11.3

Interface-Engineering Strategy for Boosting Low-Ir Catalytic Water Oxidation Using a Conductive Ti4O7 Support

Yufeng Qin,Yifan Wang,Rou Wen,Longxiang Wang,Meiling Dou,Feng Wang

The need to use expensive and scarce Ir-based catalysts in the oxygen evolution reaction (OER) hinders the large-scale application of proton exchange membrane water electrolysis (PEMWE). Herein, we present an effective interface-engineering strategy to boost the efficacy of low-Ir catalysis of OER by means of electron transfer and lattice oxygen stabilization at the catalyst–support interface by utilizing a highly conductive (∼960 S cm–1) Ti4O7 support to strongly anchor IrO2 nanoparticles. Experimental and theoretical calculations suggest that Ti4O7 tailors the Ir electronic structure that results from the formation of Ir–O–Ti bonds at the IrO2–Ti4O7 interface, resulting in a lowered d-band center that weakens the adsorption of oxygen intermediates on Ir sites and thus boosts OER catalysis. The Ir–O–Ti bonds formed at the interface stabilize lattice oxygen in IrO2, facilitating a stable lattice oxygen mechanism path for OER catalysis. The interface effect results in superior OER activity with an overpotential of 244 mV at 10 mA cm–2 and a high mass activity of 1342.9 A gIr–1 (93.25× that of commercial IrO2), and the material also shows better durability than commercial IrO2. This interface-engineering strategy affords a strong catalyst–support interaction and should facilitate the design of high-performance catalysts for PEMWE applications.

CAS / MDL: 1185-53-1
研究领域: 催化 · 材料科学 · 电化学 · 能源材料
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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

NIR-II fluorescence imaging-guided hepatocellular carcinoma treatment via IR-1061-acridine and lenvatinib co-loaded thermal-sensitive micelles and anti-PD-1 combinational therapy

Yan Du,Chunlei Shan,Yuchan You,Minjiang Chen,Luwen Zhu,Gaofeng Shu,Gang Han,Liming Wu,Jiansong Ji,Hong Yu,Yongzhong Du

Lenvatinib (LEN) combined with immune checkpoint PD-1 blockade is among the most effective treatment strategies for advanced hepatocellular carcinoma (HCC) and has been deemed a breakthrough therapy by the Food and Drug Administration. However, this combined strategy is associated with disadvantages such as non-tumor targeted aggregation and low oral bioavailability after long-term administration of LEN, and some patients show poor responses to immunotherapy as well. To overcome these drawbacks, SP94 peptide-modified thermal-sensitive micelles (SP94-poly(ethylene glycol)-poly(acrylamide- co -acrylonitrile, SP94-PEG-p(AAm- co -AN)) with an upper critical solution temperature (UCST) of 43 °C were designed. The micelles were further co-loaded with LEN and IR-1061-Acridine (IR-1061-AcD) to simultaneously achieve small molecule targeted drug, photothermal and photodynamic therapy for HCC under the guidance of near-infrared second-region (NIR-II) fluorescence imaging. After intravenous injection, the co-loaded micelles (SP94-PEG-p(AAm- co -AN)/LEN/IR-1061-AcD, SPLI) showed greater accumulation at tumor sites because SP94 has a high affinity for glucoregulatory protein 78 (GRP78), which is overexpressed on HCC cells. Given these HCC-targeted effects, SPLI appeared useful for NIR-II fluorescence imaging, enabling real-time tumor monitoring and surgical resection. In addition, SPLI could extensively induce immunogenic cell death in tumors, resulting in beneficial systemic immune responses. When further combined with anti-PD-1 immunotherapy, SPLI displayed a superior potential in suppressing tumor growth and metastasis while avoiding immune inhibition. Taken together, our study suggests that the aforementioned combinational strategy could serve as a desired multifunctional approach for HCC management.

研究领域: 肿瘤学 · 药学 · 生物医学工程 · 免疫学 · 材料科学
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DALTON TRANSACTIONS · 2022 ·Vol. 51 ·期 42 ·16119-16125 · IF 4.569

AIE-active Ir(III) complexes functionalised with a cationic Schiff base ligand: synthesis, photophysical properties and applications in photodynamic therapy

Shengnan Liu,Jiahong Han,Weijin Wang,Yulei Chang,Runlin Wang,Ziwei Wang,Guangzhe Li,Dongxia Zhu,Martin R. Bryce

Photodynamic therapy (PDT) is a promising cancer treatment method. Traditional small-molecule photosensitizers (PSs) suffer from low intersystem crossing (ISC) ability and aggregation-caused quenching (ACQ), which adversely affects the luminous efficiency and singlet oxygen (1O2) yield of PSs in the aggregated state. Ir(III) complexes are promising PSs with long excited-state lifetime, good photophysical and photochemical properties and large Stokes shifts. Aggregation-induced emission (AIE) characteristics could reduce the nonradiative recombination and improve the ISC ability of excited states through the restriction of the intramolecular motions in aggregated states. Accordingly, two AIE-active Ir(III) complexes Ir-1-N+ and Ir-2-N+ were successfully designed and obtained based on Schiff base ligands. Experimental results showed that Ir-1-N+ and Ir-2-N+ have good photophysical properties and the corresponding nanoparticles (NPs) have good water solubility and 1O2 generation ability. Notably, Ir-2-N+ NPs can be efficiently taken up by mouse breast cancer cells (4T1 cells) with good biocompatibility, low dark toxicity and excellent phototoxicity. This work demonstrates a versatile strategy for exploiting efficient transition metal PSs with a cationic ligand in PDT.

CAS / MDL: 298-93-1
研究领域: 化学 · 材料科学 · 生物医学工程 · 癌症研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH · 2022 ·Vol. 29 ·期 11 ·15337-15346 · IF 5.19

Preparation and evaluation of Pd-Sn modified Ru-Ir electrode for denitrification of high chlorine ammonia–nitrogen wastewater

Yang Zhen-xing,Shang Jie,Yan Guang-xu,Wang Yu-xian,Guo Shao-hui

In this paper, Pd-Sn modified Ru-Ir electrode was prepared by thermal oxidation method, and the effects of doping amount of Pd-Sn and synthesis conditions on Pd-Sn modified Ru-Ir electrode performance were studied. Linear sweep voltammetry(LSV), cyclic voltammetry(CV), and the Tafel curve were used to study the electrochemical performance of the Pd-Sn modified Ru-Ir electrode materials. The effects of the doping amount of Pd-Sn on the microstructure and valence states of Pd-Sn modified Ru-Ir electrode materials were investigated by SEM, TEM, XRD, and XPS. When the mass of Pd-Sn accounted for 1.5% of the total mass of the elements, the molar ratio of Ru-Ir was 2:1, and the molar ratio of Pd-Sn was 3:1; the LSV, CV, and the Tafel curves indicated that Pd-Sn modified Ru-Ir electrode had the lowest chlorine evolution potential (1.0640 V vs. SCE), the best CV curve coincidence, and the smallest corrosion current density (6.5 × 10 −4 A/cm 2 ), showing the best chlorine evolution performance, the best durability, and corrosion resistance; the characterization of SEM, TEM, XRD, and XPS showed that Pd-Sn was successfully doped into Ru-Ir electrode materials; the crystallinity of Pd-Sn modified Ru-Ir electrode was the highest, and the binding energy was the lowest, but the crystal form of Ru-Ir solid solution did not have changed. The optimal synthesis conditions of Pd-Sn modified Ru-Ir electrode material were as follows: Pd-Sn molar ratio was 3:1, calcination temperature was 500 ℃, calcination time was 4 h, and water was used as solvent. Pd-Sn modified Ru-Ir electrode can efficiently treat high chlorine ammonia–nitrogen wastewater, when the reaction volume was 200 mL, the initial concentration of NH 3 -N was 100 mg/L, the concentration of chloride ion was 5000 mg/L, the current was 0.75 A, and the reaction time was 40 min; the removal rate of ammonia nitrogen can reach 100%. Responsible editor: Weiming Zhang.

研究领域: 环境科学 · 电化学 · 材料科学 · 废水处理
✓ 已验证 产品关联 DOI PubMed 高影响因子
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DALTON TRANSACTIONS · 2023 ·Vol. 52 ·期 6 ·1595-1601 · IF 4

Self-assembled nanoparticles based on cationic mono-/AIE tetra-nuclear Ir(III) complexes: long wavelength absorption/near-infrared emission photosensitizers for photodynamic therapy

Ziwei Wang,Lijuan Li,Weijin Wang,Runlin Wang,Guangzhe Li,Hang Bian,Dongxia Zhu,Martin R. Bryce

Cyclometalated Ir(III) complexes as photosensitizers (PSs) have attracted widespread attention because of their good photostability and efficient 1O2 production ability. However, their strong absorption in the UV-vis region severely limits their applications in photodynamic therapy (PDT) because the short wavelength illuminating light can be easily absorbed by the skin and subcutaneous adipose tissue causing damage to the patient's normal tissue. Herein, mono- and tetra-nuclear Ir(III) complex-porphyrin conjugates are rationally designed and synthesized, especially [TPP-4Ir]4+ exhibits obvious aggregation-induced emission (AIE) characteristics. PSs comprising Ir(III) complex-porphyrin conjugates self-assembled as nanoparticles (NPs) are successfully achieved. The obtained [TPP-Ir]+ NPs and [TPP-4Ir]4+ NPs exhibit long wavelength absorption (500–700 nm) and near-infrared emission (635–750 nm), successfully overcoming the inherent defects of short wavelength absorption of traditional Ir(III) complexes. Moreover, [TPP-4Ir]4+ NPs exhibit good biocompatibility, high 1O2 generation ability, low half-maximal inhibitory concentration (IC50) (0.47 × 10−6 M), potent cytotoxicity toward cancer cells and superior cellular uptake under white light irradiation. This work extends the scope for transition metal complex PSs with promising clinical applications.

CAS / MDL: 298-93-1
研究领域: 材料科学 · 纳米技术 · 光动力疗法 · 癌症研究 · 光化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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