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ACS Nano · 2024 · IF 15.8

Triggered Cascade-Activation Nanoplatform to Alleviate Hypoxia for Effective Tumor Immunotherapy Guided by NIR-II Imaging

Yu Ji,Suchen Qu,Gaoyu Shi,Liansheng Fan,Jing Qian,Zhaorui Sun,Feng Lu,Xin Han

Hypoxia is one of the most typical features among various types of solid tumors, which creates an immunosuppressive tumor microenvironment (TME) and limits the efficacy of cancer treatment. Alleviating hypoxia becomes a key strategy to reshape hypoxic TME which improves cancer immunotherapy. However, it remains challenging to perform tumor precision therapy with controllable switches through hypoxia-activated gene editing and prodrugs to alleviate hypoxia. In this study, silica-coated second near-infrared window (NIR-II) emitting silver sulfide quantum dots are used as the carrier to load the Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 (CRISPR/Cas9) system to target hypoxia-inducible factor-1 (HIF-1α) and guide tumor-targeted imaging. To reduce the off-target effects in nontumor cells and better control safety risks, a TME-triggered cascade-activation nanodiagnostic and therapeutic platform (AA@Cas-H@HTS) is designed, which achieves the hypoxia activation of prodrug tirapazamine (TPZ) and spatiotemporal release of CRISPR/Cas9 ribonucleoprotein. Tumor hypoxia is greatly alleviated by the synergistic function of HIF-1α depletion by gene editing and TPZ activation. Importantly, targeting HIF-1α disrupts the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) signaling pathway, which effectively reshapes the immune-suppressive TME and activates T cell-mediated antitumor immunity. Taken together, we have provided a TME-triggered cascade-activation nanoplatform to alleviate hypoxia for improved cancer immunotherapy.

研究领域: 癌症生物学 · 免疫学 · 纳米技术 · 分子生物学 · 诊疗学
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CARBON · 2022 · IF 11.307

NIR-II sensitive Co9S8/S-CDs@PEG nanocomposites with enhanced multi-enzyme mediated phototherapy

Keke Kang,Limin Wang,Yajie Ma,Kai Yu,Jingwei Liu,Fengyu Qu,Huiming Lin

Here, Co 9 S 8 / [email protected] ( [email protected] ) nanocomposites are synthesized by a two-step hydrothermal process. Firstly, sulfur-doped carbon dots (S-CDs) are prepared by using 3-mercaptopropionic acid as a precursor. A region with denser –SH group is regarded as nucleation site on S-CDs for the growth of Co 9 S 8 to induce heterostructure. As-synthesized [email protected] possess great harvest in NIR region and hyperthermia (51.5%, 1064 nm) for photothermal (PTT). Besides, hyperthermia can elevate the thermal energy of nanocomposite to assist low-energy NIR-II irradiation (1064 nm, 1.16 eV), realizing the excitation of Co 9 S 8 (1.46 eV) and reactive oxygen species (ROS) generation for photodynamic therapy (PDT). What's more, [email protected] exhibits GOx-like activity that could consume glucose to elevate H 2 O 2 level and inhibit intracellular energy supply. In addition, they also show mimic peroxidase (POD) and catalase (CAT) characterization, and the tandem multi-nanozye activities endue the enhanced chemotherapy (CDT) and PDT. [email protected] reveals the greater ROS generation and nanozyme activity compared with pure Co 9 S 8 @PEG, attributing to the efficient charge separation in heterostructure. The novel biodegradation of [email protected] makes the elimination via feces and urine within 2 weeks. That is associated with PTT/PDT/CDT/starvation therapy to activate immune response for anticancer.

研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 癌症治疗
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Acta Biomaterialia · 2023 · IF 9.7

Gold nanobipyramid@copper sulfide nanotheranostics for image-guided NIR-II photo/chemodynamic cancer therapy with enhanced immune response

Yiyu Chen,Ping Liu,Chunze Zhou,Tao Zhang,Tianxing Zhou,Dandan Men,Guihua Jiang,Lifeng Hang

Photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) can cause cancer cell death through an immunogenic process. However, the study of second near-infrared window (NIR-II)-triggered PTT and PDT combined with CDT to induce an immune response has not been recently reported. Here, we integrated gold nanobipyramids and copper sulfide in a core/shell architecture (AuNBP@CuS). The material displays both photodynamic and photothermal properties under irradiation with a NIR-II laser. The released Cu 2+ from CuS under an acidic tumor microenvironment can be converted to Cu + by glutathione following a Fenton-like reaction with hydrogen peroxide to generate highly toxic hydroxyl radicals in the tumor region. Both in vitro and in vivo results demonstrated that such multifunctional nanoplatforms could achieve enhanced efficiency for image-guided tumor suppression based on the NIR-II photo/chemodynamic therapy. We found that damage-associated molecular pattern molecules such as adenosine triphosphate, pre-apoptotic calreticulin , and high mobility group box-1 in dying cells induced by the NIR-II photo/chemodynamic therapy could simultaneously trigger adaptive immune responses. This is the first report revealing that NIR-II photo/chemodynamic therapy based on AuNBP@CuS had promising performance on tumor suppressor with an effective immunogenic cell death process. Statement of significance 1. AuNBP@CuS displays both NIR-II photodynamic and photothermal properties. 2. Cu + following a Fenton-like reaction to generate highly toxic hydroxyl radicals. 3. The NIR-II photo/chemodynamic therapy can trigger adaptive immune responses. 4. Such multifunctional nanoplatforms could achieve enhanced efficiency for tumor suppression.

研究领域: 肿瘤学 · 纳米医学 · 生物材料学
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CHEMICAL ENGINEERING JOURNAL · 2019 · IF 8.355

Boosting phototherapeutic efficiency with single NIR laser-activated ultrasmall bismuth sulfide quantum dots

Huayan Yang,Yanmin Zhang,Jian Song,Meng Wang,Shaoning Yu,Liang Chen,Xiaomin Li,Shouning Yang,Lin Yang

The integration of photothermal therapy (PTT) with photodynamic therapy (PDT) has great potential to revolutionize conventional therapeutic approaches for cancers. However, most of the currently developed nanoplatforms for combinatorial phototherapy require the participation of different components or activation of separate lasers. Therefore, a desirable photoactive agent with intrinsic single laser-activated combinatorial phototherapy is still urgently needed for more efficient treatment. Here, we demonstrate a high-temperature organic synthesis, ligand exchange strategy to obtain ultrasmall, water-dispersible, and stable polylysine-bismuth sulfide quantum. dots (PLL-Bi 2 S 3 QDs). In addition to its strong near-infrared (NIR) absorption, the ultrasmall size and sulfide-enriched surface of the obtained Bi 2 S 3 QDs offer abundant photoelectrons with high reducing ability, promoting the rapid generation of reactive oxygen species (ROS). Therefore, excellent photothermal conversion and fast ROS generation ability can be concurrently realized upon 808 nm NIR laser irradiation. As proof of concept, the combined photothermal/photodynamic activity in single PLL-Bi 2 S 3 QDs was demonstrated both in vitro and in vivo , confirming that the phototherapeutic efficacy is dramatically greater than that of larger Bi 2 S 3 nanorods. In addition, toxicity screening showed that PLL-Bi 2 S 3 QDs possess excellent biocompatibility. Thus, the prepared PLL-Bi 2 S 3 QDs are expected to serve as a photoactive agent for efficient cancer treatment.

研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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Nano Today · 2024 · IF 13.2

NIR-II light-activated and Cu nanocatalyst-enabled bioorthogonal reaction in living systems for efficient tumor therapy

Hui Huang,Wendi Xuan,Jiakang Hai,Xue Wang,Meng Chen,Guobing Hong,Xinyue Dai,Lili Xia,Wei Feng,Yu Chen

Bioorthogonal reaction refers to chemical reactions that occur within a biological system without interfering the normal biochemical process, offering the unprecedented versatility in engineering chemical reactions within cells. However, the precise regulation of bioorthogonal reaction in living systems is mired by the complexity of the physiological environment and the toxicity of catalysts. Herein, considering the deeper tissue penetration and reduced phototoxicity compared to visible light and ultraviolet, a second near infrared (NIR-II) light-activated Cu-based bioorthogonal reaction is developed to achieve precise spatiotemporal control and effective switching for Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) mediated chemical transformations in tumor, reducing the off-target effects. The catalytic activity of Cu catalyst through valence state interconversion between Cu(II) and Cu(I) can be precisely regulated in a reversible manner under NIR-II light irradiation-induced photoelectron transfer, which controls the extent of desired drug synthesis in bioorthogonal reaction. Meanwhile, the adverse effects of Cu(I) can be substantially mitigated within normal tissues due to their oxygen-rich condition. By utilizing NIR-II light and oxygen level, the Cu bioorthogonal catalyst achieves a balance between catalytic activity and biocompatibility. The ability to achieve precise spatiotemporal control and reversible catalysis makes this NIR-II light-mediated CuAAC platform an efficient and adaptable tool for bioorthogonal chemistry in living systems.

研究领域: 生物医学工程 · 癌症治疗 · 纳米技术 · 光化学 · 药学
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Small · 2024 · IF 13

Ultrasensitive NIR-II Surface-Enhanced Resonance Raman Scattering Nanoprobes with Nonlinear Photothermal Effect for Optimized Phototheranostics

Laicui Song,Jin Li

Surface-enhanced resonance Raman scattering (SERRS) in the second near-infrared (NIR-II) window has great potential for improved phototheranostics, but lacks nonfluorescent, resonant and high-affinity Raman dyes. Herein, it is designed and synthesize a multi-sulfur Raman reporter, NF1064, whose maximum absorption of 1064 nm rigidly resonates with NIR-II excitation laser while possessing absolutely nonfluorescent backgrounds. Ultrafast spectroscopy suggests that the fluorescence quenching mechanism of NF1064 originates from twisted intramolecular charge transfer (TICT) in the excited state. Gold nanorods (AuNRs) decorated with such nonfluorescent NF1064 (AuNR@NF1064) show remarkable SERRS performances, including zero-fluorescence background, femtomolar-level sensitivity as well as superb photostability without fluorescence photobleaching. More importantly, AuNR@NF1064 exhibits a nonlinear photothermal effect upon plasmonic fields of AuNRs by amplifying the non-radiative decay of nonfluorescent NF1064, thus achieving a high photothermal conversion of 68.5% in NIR-II window with potential for further augmentation. With remarkable SERRS and photothermal properties, the NIR-II nanoprobes allow for high-precision intraoperative guided tumor resection within 8 min, and high-efficient hyperthermia combating of drug-resistant bacterial infection within living mouse body. This work not only unlocks the potential of nonfluorescent resonant dyes for NIR-II Raman imaging, but also opens up a new method for boosting photothermal conversion efficiency of nanomaterials.

CAS / MDL: 62-31-7
研究领域: 生物医学工程 · 纳米医学 · 光学成像 · 光热治疗
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Advanced Optical Materials · 2025 · IF 7.2

Engineering Ho3+-Mediated Energy Transfer for Enhanced Pr3+ NIR-II Luminescence in Core–Shell Nanocrystals toward Ultrasensitive Temperature Sensing

Kejie Li,Haikuo Liu,Zhiying Wang,Mengmeng Dai,Jiaqi Zhao,Zuoling Fu

Near-infrared II (NIR-II, 1000–1700 nm) luminescence has emerged as a powerful tool for biomedical applications, including sensing, imaging, and drug delivery, owing to its superior tissue penetration depth and high spatial resolution. Lanthanide-based NIR-II nanoprobes are particularly promising due to their outstanding photostability and minimal cytotoxicity. However, two critical challenges impede their widespread implementation: severe thermal quenching at elevated temperatures and inefficient downshifting processes. Herein, a novel strategy is reported to address these limitations by precisely modulating energy transfer dynamics between Ho 3+ and Pr 3+ ions in NaYF 4 core–shell engineering. By carefully optimizing the concentration ratio and spatial distribution of these lanthanide ions in NaYF 4 core–shell nanocrystals, the population of 1 G 4 (Pr 3+ ) is significantly increased, effectively suppressing thermal quenching while boosting downshifting efficiency. The optimized system leverages dual NIR-II emission channels ( 1 G 4 and 5 I 6 ) in NaYF 4 :Yb 3+ /Ho 3+ @NaYF 4 :Yb 3+ /Pr 3+ nanocrystals, enabling ultrasensitive temperature sensing with a maximum relative sensitivity ( S r ) of 2.03% K −1 . Furthermore, the synergistic up/down-conversion properties of Ho 3+ and Pr 3+ facilitate multimodal anti-counterfeiting, offering a robust platform for advanced information encryption and storage. This work not only establishes a new paradigm for engineering NIR-II luminescence but also underscores their vast potential in advanced applications, from precision biosensing to high-security encoding technologies.

研究领域: 纳米技术 · 材料科学 · 生物医学工程 · 光学 · 传感器 · 发光
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 19 ·4274-4286 · IF 7

Dual enzyme-like Co–FeSe2 nanoflowers with GSH degradation capability for NIR II-enhanced catalytic tumor therapy

Jingge Zhang,Enna Ha,Danyang Li,Shuqing He,Luyang Wang,Shaolong Kuang,Junqing Hu

Nanozymes mediated catalytic therapy can produce toxic reactive oxygen species (ROS) and destroy the metabolic balance of tumor cells, providing a new direction for cancer treatment. However, the catalytic efficiency of a single nanozyme is limited by the complexity of the tumor microenvironment (hypoxia, GSH overexpression, etc.). In order to overcome these problems, we designed flower-like Co-doped FeSe2 (Co–FeSe2) nanozymes by a simple wet chemistry method. Co–FeSe2 nanozymes not only exhibit high POD and OXD-mimicking activities for facile kinetics, but also effectively consume over-expressed glutathione (GSH), inhibiting the consumption of generated ROS and destroying the metabolic balance of the tumor microenvironment. These catalytic reactions trigger cell death through apoptosis and ferroptosis dual pathways. More importantly, under the NIR II laser irradiation, the catalytic activities of Co–FeSe2 nanozymes are boosted, confirming the photothermal and catalytic synergistic tumor therapy. This study takes advantage of self-cascading engineering that offers new ideas for designing efficient redox nanozymes and promoting their clinical translation.

研究领域: 癌症治疗 · 材料科学 · 纳米医学 · 生物化学
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CHEMICAL ENGINEERING JOURNAL · 2020 · IF 10.652

An NIR-II light responsive antibacterial gelation for repetitious photothermal/thermodynamic synergistic therapy

Qinzhe Li,Yewei Zhang,Xuan Huang,Dongliang Yang,Lixing Weng,Changjin Ou,Xuejiao Song,Xiaochen Dong

Drug-resistant bacterial infection is a serious threat to the survival and health of human. Clinically, the conventional therapy for subcutaneous infections generally involves the systemic administration of high dose of antibiotics and frequently causes detrimental side effects in normal tissues. To overcome this issue, an acidity-responsive near infrared (NIR) light-triggered injectable hydrogel was designed for non-antibiotic local treatment. Herein, poly(ethylene glycol) diacrylate (PEGDA) was used as hydrogel matrix, polyoxometalate (POM) as acidity-enhanced photothermal agent and 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydro-chloride (AIPH) as thermo-responsive initiator. After the hydrogel precursor solution (AIPH/POM/PEGDA) was injected into the acidic infected tissue, the aggregated POM with strong photothermal property was restricted to the site of abscess. Upon excitation at 1060 nm laser, the heat generated from POM would trigger alkyl radical formation from AIPH and thereafter achieving NIR-triggered in situ gel. Consequently, the POM and AIPH were trapped in Gel(AIPH/POM) and exhibited long-term retention in the abscess for further repeated local photothermal/thermodynamic antibacterial therapy. In vitro antibacterial evaluation indicated that the system could effectively eradicate drug-resistant bacteria through destroying bacteria integrity and producing the noxious alkyl radical under NIR light illumination. Moreover, the bacterial burden of abscess was significantly relieved and more collagens were deposited after the administration of Gel(AIPH/POM) and repeated NIR light. Meanwhile, no apparent adverse effect was observed during the treatment. This work not only provides a light-triggered gelation for local photothermal/thermodynamic synergistic therapy, but also offers a novel strategy for the rational design of light-responsive intelligent antibacterial hydrogels.

研究领域: 生物医学工程 · 药学 · 材料科学 · 抗菌治疗 · 光热治疗 · 智能药物递送系统
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Advanced Healthcare Materials · 2023 · IF 10

NIR-II Regulation of Mitochondrial Potassium Channel with Dual-Targeted Conjugated Oligomer Nanoparticles for Efficient Cancer Theranostics In Vivo

Chaoqun Li,Dong Gao,Yijian Gao,Ran Zhang,Xiongwei Qu,Shengliang Li,Chengfen Xing

Cell fate can be efficiently modulated by switching ion channels. However, the precise regulation of ion channels in cells, especially in specific organelles, remains challenging. Herein, biomimetic second near-infrared (NIR-II) responsive conjugated oligomer nanoparticles with dual-targeted properties are designed and prepared to modulate the ion channels of mitochondria to selectively kill malignant cells in vivo. Upon 1060 nm laser irradiation, the mitochondria-located nanoparticles photothermally release a specific ion inhibitor of the potassium channel via a temperature-sensitive liposome, thus altering the redox balance and pathways of mitochondria. NIR-II responsive nanoparticles can effectively regulate the potassium channels of mitochondria and fully suppress tumor growth. This work provides a new modality based on the NIR-II nanoplatform to regulate ion channels in specific organelles and proposes an effective therapeutic mechanism for malignant tumors.

研究领域: 纳米技术 · 癌症生物学 · 诊疗学 · 生物医学工程
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Thrombin and NIR dual-responsive system driven by heat-gas for thrombus targeted therapy

Huijuan Zhang,Kexuan Cao,Chaoqun Wang,Yingmei Tian,Lin Hou

Drug thrombolysis is the main means of clinical treatment for thrombotic-related diseases. However, serious bleeding complications caused by low drug delivery efficiency and secondary vascular embolism usually lead to unsatisfactory therapeutic effects. Herein, we constructed a thrombin and near-infrared (NIR) dual-responsive drug-loaded intelligent system to solve the above problems. The CREKA-modified polydopamine (PDA) nanoparticles (NPs) were crosslinked by thrombin-responsive peptide (Pep), to obtain Pep-PPC nanocarriers with special mesoporous nanostructures. Subsequently, NO donor BNN6 and thrombolytic drug UK were loaded on the surface and into the mesoporous of Pep-PPC, to get the multifunctional Pep-NO@PPC/UK. In vitro and in vivo results proved that Pep-NO@PPC/UK could effectively recognize and aggregate at the thrombus site via CREKA-mediated active targeting. Then local abundant thrombin cleaved the nanoplatform to release UK. Meanwhile, PDA converted NIR light into heat and synchronously triggered NO release. This transformed the DDS into a “heat-gas” dual propulsion nanomotor in situ, driving deep penetration of UK in thrombus tissue. Under the combined action of UK and PTT, arterial thrombosis rapidly dissolved with relatively low bleeding risk. More importantly, NO generated in situ could prevent re-embolism of blood vessels at the thrombolytic site by inhibiting activated platelet aggregation, ultimately improving vascular reperfusion rate through a combination of attack and defense mode.

研究领域: 药学 · 纳米技术 · 生物医学工程 · 治疗学
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NEW JOURNAL OF CHEMISTRY · 2023 · IF 3.3

Doping Ag2S quantum dots with Pb yields significantly enhanced in vivo fluorescence imaging in the NIR-II window and comparable toxic effects

Qingyuan Cheng,Liman Li,Mingxia Yu

Silver chalcogenide (Ag2X; X = S, Se, Te) quantum dots (QDs) have facilitated the biomedical applications of QDs due to their low toxicity and tunable emission reaching the second near-infrared window (NIR-II window, 1000–1700 nm). The photoluminescence intensity of Ag2S QDs and Ag2Se QDs is considerably enhanced via Pb doping. However, the developed Pb-doped Ag2S QDs lacked in vivo verification, and the toxicity of the Pb-doped Ag2X QDs was only preliminarily assessed. Although QDs containing Pb have been widely introduced into the field of biomedicine, there are still concerns regarding toxicity associated with Pb. In the present study, we prepared polyethylene glycol (PEG)-modified Pb-doped Ag2S QDs with better biocompatibility and tested their in vivo bioimaging and toxicity in comparison with Ag2S QDs modified with the same PEG under identical concentrations. Results indicated that the PEG-modified Pb-doped Ag2S QDs significantly enhanced the brightness of in vivo bioimaging and spatial resolution for vessels inside the tumor without increasing toxicity, assessed based on cell viability post incubation for 96 h, intracellular ROS level, DNA damage, early apoptosis and mitochondrial injury. Our study demonstrated that the PEG-modified Pb-doped Ag2S QDs could serve as an advanced fluorescent probe for various biomedical applications.

研究领域: 生物医学工程 · 材料科学 · 纳米技术 · 毒理学
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