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NIR II成像
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
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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
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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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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Donor Substitution Engineering of Hemicyanine Nanoparticles to Reprogram the Tumor Microenvironment and Enhance Fn14-Targeted BiTE for Glioblastoma Photoimmunotherapy

Gaowei Li,Shichao Jiang,Zongliang Zhang,Xiaoyin Liu,Kai Wu,Peng Liu,Mei Yang,Ting Zhou,Jiamei Xiao,Nini Xin,Xiaoyang Wu,Zhihong Chen,Jie Ding,Chengheng Wu,Dan Wei,Jing Sun,Aiping Tong,Hongsong Fan,Liangxue Zhou

Glioblastoma (GBM) is a highly malignant intracranial tumor with limited treatment options. Bispecific T-cell engagers (BiTEs) are being explored for GBM treatment, but their success is hindered by inadequate T cell infiltration and activation due to the acidic and immunosuppressive microenvironment. Photothermal immunotherapy lyses tumors and activates immune responses, complementing BiTEs. This study innovatively employs a donor engineering strategy to develop hemicyanine dyes (Hcys) that emit from near-infrared (NIR) I to NIR II. The Hcy with excellent properties is encapsulated in an amphiphilic micelle, forming a nano assembly with lactate oxidase (PLH1100). PLH1100 exhibits spectral absorption at 980 nm, a photothermal conversion efficiency of 58.7%, and capability for NIR-II tumor imaging. Besides photothermal tumor ablation, PLH1100 regulates lactic acid metabolism and activates immunogenic cell death, improving the tumor microenvironment and promoting T cell infiltration and activation. Further studies demonstrate PLH1100 effectively kills human and murine GBM cells, inhibits orthotopic U87 tumor growth in BALB/c-nu mice, and enhances the efficacy of Fn14-targeted BiTE in orthotopic GL261 tumors in C57BL/6 mice, achieving a synergistic “1+1>2” therapeutic effect. Collectively, this work opens a new pathway for using Hcy-based molecules combined with BiTE drugs for GBM therapy, with significant clinical potential.

研究领域: 肿瘤学 · 纳米技术 · 免疫疗法 · 分子生物学 · 神经科学
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