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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

In vivo imaging tool: High-brightness NIR-II “J-aggregates” based on TICT suppression strategy

Taihe Han,Shuai Mu,Qin Huang,Jiaxing Sun,Xin Lv,Yanxia Zhang,Xiaoyan Liu,Wei Guo,Haixia Zhang

The development of high fluorescence quantum yield molecular fluorophores for second-order near-infrared (NIR-II) imaging is highly desirable but remains challenging due to the lack of reliable design guidelines. We report a method to construct “J-aggregates” by combining the inhibition of twisted intramolecular charge transfer (TICT) and electron-withdrawing strategies. Introducing electron-withdrawing substituents at the middle position of the classic boron dipyrromethene (BODIPY) backbone promotes J-type slip stacking, enhancing NIR-II fluorescence through increased electrostatic repulsion and intermolecular hydrogen bonding. The 3,5-aryl position is modified with sulfone and quaternary piperazine groups. The negative inductive effect (–I effect) from strong electron-withdrawing action increases the ionization potential (IP) of the amino group, inhibiting the TICT process and improving the quantum yield to 9.03 % and 16.9 %, respectively. Notably, the fluorescence quantum yield of NBDP-SO 2 increased to 18.2 % after self-assembly with F127, successfully applied in bioimaging. This study provides a new method for constructing high fluorescence quantum yield NIR-II emission by manipulating molecular stacking and establishing the relationship between molecular structure, intermolecular interactions, and fluorescence properties.

研究领域: 生物医学工程 · 分子影像学
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Theranostics · 2025 ·Vol. 15 ·期 10 ·4481 · IF 13.3

Two-plex in vivo molecular imaging in the second near-infrared window for immunotherapeutic response

Yupeng Sun,Rui Li,Yike Cai,Yan Liu,Peiyuan Wang,Ming Wu,Xiaolong Zhang,Naishun Liao,Cuilin Zhang,Aixian Zheng,Haipo Xu,Rui Zeng,Yongyi Zeng,Xiaolong Liu

Tumor-infiltrating CD8 + T cells and programmed death-1 (PD1) levels are critical indicators for tumor immunophenotyping and therapeutic decision-making. Noninvasive optical imaging in the second near infrared window (NIR-II) is particularly well-suited for investigating the biological processes within tumors in live mammals, thanks to its deep-tissue penetration and superior spatiotemporal resolution. However, in vivo NIR-II imaging has primarily been restricted to a single probe at a time. Methods: Herein, we developed a two-plex NIR-II molecular imaging method utilizing the non-overlapping fluorescence emission of indocyanine green (ICG) in the NIR-IIa window (1000-1200 nm) and PbS/CdS core-shell quantum dots (QDs) in the NIR-IIb window (1500-1700 nm). By integrating PD1 aptamer-labeled ICG (ICG-Apt-PD1, targeting PD1) and CD8 aptamer-labeled QDs (QDs@Apt-CD8, targeting CD8 + T cells), our two-plex NIR-II molecular imaging enabled simultaneous and noninvasive monitoring of the number of CD8 + T cells and PD1 levels in tumors. Results: QDs@Apt-CD8 demonstrated the excellent ability for in vivo imaging of tumor infiltrating CD8 + T cells, owing to its strong NIR-IIb luminescence and the high selectivity and specificity. This two-plex in vivo molecular imaging allowed for dynamic monitoring for PD1 levels and the number of CD8 + T cells in tumors. We observed the heterogeneous bio-distributions of PD1 and CD8 + T cells across different tumor types and revealed the tumor immunophenotypes. Moreover, our findings indicated that the low PD1 and high CD8 + T cells levels in tumors predicted a better anti-tumor effect. Conclusions: Such in vivo noninvasive NIR-II molecular imaging would complement ex vivo biopsy-based diagnostic techniques, and it could contribute to developing an in vivo tumor immune-scoring algorithm to offer a more precise prediction for immunotherapeutic response.

CAS / MDL: 112-90-3 112-80-1
研究领域: 生物医学工程 · 肿瘤免疫学 · 分子影像学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR IMAGING AND BIOLOGY · 2023 ·Vol. 25 ·期 5 ·875-886 · IF 3.1

Nd-Mn Molecular Cluster with Searched Targets for Oral Cancer Imaging

Hui Xin,Wang Yanxing,Li Wenjing,Yuan Ying,Tao Xiaofeng,Lv Ruichan

In this research, we designed a novel NIR II luminescence imaging probe with targeting effect to accurately track oral squamous cell carcinoma (OSCC) cells. Massive gene expression data were processed by weighted gene co-expression network analysis to establish a network of relationships between genes. After clustering, correlation of clinical information, and gene functional enrichment analysis, MMP1 was predicted to be a biomarker/therapeutic target for OSCC cells. To obtain rare-earth probes with better luminescence in the NIR II region, we adjusted the doping ratio of the rare-earth element (Nd, Gd, Er, and Yb) fraction of the Nd-Mn molecular cluster to optimize its luminescence properties. The results of in vitro targeting experiments showed that Nd-Mn-MMP1Ab can target Cal-27 cells, demonstrating at the cellular level that the MMP1 gene is a biomarker for oral cancer, which also proves that the cancer targets predicted by the bioinformatics approach are correct.

研究领域: 生物信息学 · 癌症研究 · 分子影像学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

NIR-II multiplexed fluorescence imaging of bacteria based on excitation-selective lanthanide-doped core-shell nanoparticles

Leilei Sun,Yao Huang,Chenhui Ji,Craig A. Grimes,Qingyun Cai

Physiological processes and bacterial infection can be effectively monitored using multiplexed imaging in the second near-infrared region (NIR-II). In this study, we design two lanthanide-doped core-shell (cs) nanoparticles , NaYF 4 :Nd,Yb@NaYF 4 (csNd,Yb) with 980 and 1060 nm emission under 808 nm excitation, and NaYF 4 :Yb,Er,Ce@NaYF 4 (csYb,Er,Ce) with 1525 nm emission under 980 nm excitation. The NIR-II emission spectra of the two nanoparticles do not overlap. XRD characterization shows that the nanoparticles have good crystallinity . The nanoparticles are surface modified with vancomycin (Van) and polymyxin B (PMB), which can respectively target Gram-positive and Gram-negative bacteria for specific imaging and bacteria differentiation. In vitro experiments confirm that csNd,Yb-PMB and csYb,Er,Ce-Van can be used to detect different types of bacteria. In vivo simultaneous multiplexed NIR-II imaging of Gram-positive/negative bacterial infection is demonstrated. The good biocompatibility of the nanoprobes is demonstrated by MTT assay, monitoring the distribution in major organs at different times, and histological analysis .

研究领域: 生物医学工程 · 材料科学 · 微生物学
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Advanced Science · 2025 · IF 14.1

Potentiating the Efficacy of mRNA Vaccines through NIR-II Imaging-Guided Precise Vaccination

Mengfei Li,Xue Zheng,Xinyang Yu,Shaolong Qi,Shoujun Zhu,Guocan Yu,Songling Zhang

mRNA vaccines have been widely implemented and revolutionized the landscape of oncology and epidemiology. Potent vaccination demands precise control over injection depth to ensure optimal lymphatic drainage, driving the development of non-invasive imaging techniques to visualize the distribution and efficacy of mRNA vaccines. Herein, near-infrared-II (NIR-II) lipid nanoparticles (NIR-II-LNPs) are fabricated for mRNA delivery by integrating a cationic fluorophore amphiphile (IR780-C16) into traditional LNPs, enabling longitudinal, quantitative, and non-invasive trafficking of mRNA vaccines. The in vivo behaviors of mRNA vaccines are characterized with different vaccination protocols in mice and rabbits by NIR-II fluorescence imaging. Results proved that following a 25 µL injection of mRNA vaccines into the mouse thigh at a depth of 4 mm or a 500 µL injection volume into a rabbit at a depth of 7 mm via the intramuscular route, the vaccines rapidly and abundantly accumulated in the inguinal lymph nodes. Flow cytometry and tissue immunofluorescence analyses further validated that optimized vaccination parameters effectively activated antitumor immunity and greatly boosted the therapeutic efficacy in B16-OVA and HPV-associated mouse tumor models. NIR-II-LNPs offer a unique modality for non-invasively monitoring the fate of vaccines, reinforcing its role in preclinical and clinical mRNA therapeutics.

研究领域: 肿瘤学 · 免疫学 · 生物医学工程 · 分子成像 · 疫苗学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Science · 2023 · IF 6.6

NIR-II imaging-guided photothermal cancer therapy combined with enhanced immunogenic death

Yukun Wang,Wenjing Li,Bi Lin,Ying Yuan,Pengbo Ning,Xiaofeng Tao,Ruichan Lv

Photothermal therapy has a remarkable effect on the destruction of tumors. It kills tumor cells by photothermal ablation and induces immunogenic cell death by activating the immune response in tumor tissues. However, inhibition of the tumor immune microenvironment suppresses PTT-induced body-specific anti-tumor immunity. In this study, we designed the GdOF@PDA-HA-R837-hydrogel complex to achieve NIR-II imaging-guided photothermal ablation and enhanced immune response. Due to the doping of Yb and Er elements and the presence of a polydopamine coating, the synthesized nanoparticles enable NIR-II and photoacoustic imaging of tumor tissues, which will help in the integration of multimodal tumor imaging for diagnosis and treatment. Polydopamine is used as a photothermal agent and drug carrier because of its excellent photothermal ability and high drug loading capacity under 808 nm near infrared light. Hyaluronic acid can bind to specific receptors on the surface of cancer cells, allowing nanoparticles to aggregate around the tumor, thus enhancing the targeting ability of nanoparticles. In addition, imiquimod (R837) has been used as an immune response modulator to enhance the immunotherapeutic effect. The presence of a hydrogel enhanced the retention effect of nanoparticles in the tumor. We demonstrate that the combination of photothermal therapy with immune adjuvants effectively induces ICD, which in turn stimulates the activation of specific anti-tumor immunity and enhances the effect of photothermal therapy in vivo.

研究领域: 肿瘤学 · 生物医学工程 · 纳米医学 · 免疫治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Cancer Cell International · 2020 ·Vol. 20 ·期 1 ·1-16 · IF 4.175

Targeted nanobody complex enhanced photodynamic therapy for lung cancer by overcoming tumor microenvironment

Zhang Qing,Wu Lian,Liu Shaozheng,Chen Qingjie,Zeng Lingpeng,Chen Xuezhong,Zhang Qing

Background To investigate the efficacy of a PLGA-based nanobody complex in photodynamic therapy (PDT) and NIR-II imaging in A549 tumor hypoxic model.MethodIR1048-MZ was firstly synthesized by conjugating a nitro imidazole group to IR1048. IR1048-MZ and Cat were then encapsulated in PLGA-SH solution. Anti-EGFR-Nanobody was also expressed and purified, and finally Anti-EGFR-Nanobody@PLGA-IR1048MZ-Cat (Nb@IC-NPs) nanobody complex was obtained based on the formation of desulfide bond between PLGA-SH and Anti-EGFR-Nanobody. Size distribution and morphology were characterized by TEM and DLS. Spectrum of Nb@IC-NPs towards NTR was measured by UV and fluorescence, while the particle’s selective response was studied using fluorescence. The uptake of Nb@IC-NPs in A549 cells was observed by flow cytometry and CLSM. In the meantime, its’ catalytic ability that decomposes H2O2 both extra-and intra-cellular was observed by fluorescence and CLSM. In vitro photodynamic toxicity of Nb@IC-NPs was examined by MTT, Live/Dead Cell Staining, Flow Cytometry and Apoptosis Assay. Tumor-bearing model was constructed to observe a semi-quantitative fluorescent distribution and the possibility of NIR-II fluorescence/photoacoustic (PA) imaging. Effect of Nb@IC-NPs on enhancing A549 tumor hypoxia and expression profile of HIF-1α was investigated in the presence of NIR. An A549 tumor metastasis model was also constructed to confirm the complex’ potential to destroy primary tumor, inhibit lung metastasis, and prolong mice’ survival. Lastly, impact of Nb@IC-NPs on mice’ main organs and blood indices was observed.Results Nb@IC-NPs was successfully fabricated with good homogeneity. The fluorescent absorbance of Nb@IC-NPs showed a linear relationship with the concentration of NTR, and a higher concentration of NTR corresponded to a stronger photoacoustic signal. In addition, Nb@IC-NPs showed a stable selectivity toward NTR. Our results also suggested a high efficient uptake of Nb@IC-NPs in A549 cells, which was more efficient than IC-NPs and IR1048-MZ alone. In vitro assays confirmed the effects of Nb@IC-NPs on catalytic O2 generation even in hypoxic cells. The cell viability was upregulated with the nanocomplex at the absence of the laser, whereas it was dramatically declined with laser treatment that excited at 980 nm. Nb@IC-NPs achieved tumor hypoxia NIR-II/PA imaging through assisting A549 gathering. When NIR was applied, Nb@IC-NPs can significantly relieve A549 cellular/tumor hypoxia by generating more reactive oxygen species (ROS), which in turn helps lower the expression level of HIF-1α. In summary, Nb@IC-NPs based PDT can efficiently decimate A549 primary tumor, inhibit metastatic lung cancer, and prolong the lifespan of the mice under tolerable dosage. At last, in vivo toxicity tests of the nanocomplex showed its biosafety to the main organs and normal blood indices values.Conclusion Nb@IC-NPs improves tumor hypoxia through catalytic reaction and lowers the expression level of HIF-1α. It achieves tumor PA imaging through intensified NIR-II fluorescence signal that caused by response of the complex to the lesion’s nitroreductase (NTR). Nb@IC-NPs based PDT can efficiently kill A549 primary tumor, inhibit a lung metastasis, as well as prolong mice’ survival cycle.

CAS / MDL: 9001-05-2
研究领域: 癌症研究 · 生物医学工程 · 药学 · 分子生物学 · 成像科学
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BIOMATERIALS · 2020 · IF 10.317

Novel ultrasmall multifunctional nanodots for dual-modal MR/NIR-II imaging-guided photothermal therapy

Fenfen Li,Tuanwei Li,Debo Zhi,Pengping Xu,Wenshen Wang,Yi Hu,Yuanyuan Zhang,Shaozhen Wang,J. Matula Thomas,J. Beauchamp Norman,Weiping Ding,Lifeng Yan,Bensheng Qiu

Encouraging progress in multifunctional nanotheranostic agents that combine photothermal therapy (PTT) and different imaging modalities has been made. However, rational designed and biocompatible multifunctional agents that suitfable for in vivo application is highly desired but still challenging. In this work, we rationally designed novel ultrasmall multifunctional nanodots (FS-GdNDs) by combining the bovine serum albumin (BSA)-based gadolinium oxide nanodots (GdNDs) obtained through a biomineralization process with a small-molecule NIR-II fluorophore (FS). The as-prepared FS-GdNDs with an ultrasmall hydrodynamic diameter of 9.3 nm exhibited prominent NIR-II fluorescence properties, high longitudinal relaxivity (10.11 mM −1  s −1 ), and outstanding photothermal conversion efficiency (43.99%) and photothermal stability. In vivo studies showed that the FS-GdNDs with enhanced multifunctional characteristics diaplayed satisfactory dual-modal MR/NIR-II imaging performance with a quite low dose. The imaging-guided PTT achieved successful ablation of tumors and effectively extended the survival of mice. Cytotoxicity studies and histological assay demonstrated excellent biocompatibility of the nanodots. Importantly, this novel FS-GdNDs can undergo efficient body clearance through both hepatobiliary and renal excretion pathways. The novel ultrasmall multifunctional FS-GdNDs with excellent features hold tremendous potential in biomedical and clinical applications.

研究领域: 纳米技术 · 生物医学工程 · 诊疗学 · 分子影像
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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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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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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

Dual-modality imaging particle size monodisperse poly (ethylene glycol) diacrylate drug-loaded embolic microspheres for tumor therapy

Luping Chen,Shixiang Liu,Fengyuan Gao,Hailin Cong,Bing Yu,Youqing Shen

Transcatheter arterial chemoembolization (TACE) is one of the common methods of treating tumors and usually requires an accompanying injection of an exogenous contrast agent, but the exogenous contrast agent is highly susceptible to removal by blood flow , which greatly reduces the efficiency of the operation. Here, we developed a uniformly sized Ag 2 S/BaSO 4 /DOX@PEGDAMS that integrates embolization, drug loading, and visualization with a microfluidic device . The microspheres can be imaged stably under NIR-II/X-ray for a long time, and the luminescence of NIR-II is better than that of X-ray. This breaks the limitations of conventional X-ray-only imaging of embolic microspheres . The microscope images and scanning electron microscope EDS results showed that the microspheres were regularly spherical with uniform particle size, and the signature elements such as Ag, S, and Ba were uniformly distributed in the microspheres. In vitro cytotoxicity assays and apoptosis assays have demonstrated that the microspheres have good biocompatibility and can effectively inhibit tumor cell growth due to the presence of DOX. The ability of microspheres to aggregate in blood vessels and block blood flow was verified by modeling and embolizing in rabbit ear tumors. In conclusion, Ag 2 S/BaSO 4 /DOX@PEGDAMS shows excellent embolization, drug loading, and imaging capabilities, and has the potential to be used for TACE and other diseases requiring interventional embolization therapy.

CAS / MDL: 298-93-1 9002-93-1
研究领域: 生物医学工程 · 药学 · 癌症治疗 · 材料科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

Near-infrared fluorescent probes for non-invasive, real-time, and dual-color in vivo NIR-II imaging

Huixian Jia,Yujie Liu,Wei Tang,Chenghui Liu,Xinrui Duan

Multiplexed fluorescence imaging is mainly applied to cellular imaging. However, the application of an analogous technique to mammals remains challenging due to the presence of substantial scattering and autofluorescence in biological tissues in the visible (350–700 nm) and near-infrared I region (NIR-I, 700–900 nm). Herein, we report multiplexing excitation and single-channel detection in the near-infrared II region (NIR-II) with two fluorescent probes for dual-color imaging in vivo. The first one, FNIR-1090 was constructed on Pr-1099 derivative by attaching with 1-Ethylpiperazine through the SRN1 displacement reaction. The second one, IR-765 was synthesized by a one-step reaction between the Vilsmeier–Haack reagent with 2-(3,5,5-trimethylcyclohex-2-enylidene) malononitrile (TEMO). It is noteworthy that the absorption spectrum of FNIR-1090 is almost completely separated from that of IR-765, which facilitates dual-color in vivo imaging. The two dyes can be used for high-contrast dual-channel vivo imaging of different tissues. All these prominent performances show the great promise of FNIR-1090 and IR-765 in non-invasive, real-time, and dual-color NIR-II imaging (>900 nm) in vivo.

CAS / MDL: 130-00-7 9005-64-5
研究领域: 生物医学工程 · 分子成像 · 光学成像
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