ACS Nano
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2024
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IF 15.8
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.
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Small
·
2024
·
IF 13
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.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-12
·
IF 15.7
Ye Miantai,Wang Xiaoyu,Zou Jingwen,Sun Wei,Chi Weijie,Mao Zhiqiang,Liu Zhihong
The second near-infrared (NIR-II) dyes provide advantages for in vivo imaging, but challenges persist. A primary issue is the lack of practicable strategies to balance emission wavelength and molecular weight, particularly for low-molecular-weight (<500 Da) NIR-II (λ em > 1000 nm) dyes. Here, we propose a strategy that tunes NIR-II emissions by reducing Coulomb attraction interaction, contrasting with traditional approaches that redshift absorption wavelengths through energy gap reduction. Leveraging this concept, we extend the emission wavelength of GFP chromophore-based dyes LS1-12 from the visible range into the NIR-II region, achieving a maximum emission wavelength exceeding 1200 nm with molecular weights between 226 and 449 Da. Further, the optimized NIR-II dye LS7 selectively binds Aβ 42 fibrils, yielding a 22.7-fold fluorescence increase in vitro and enabling real-time imaging of deposited Aβ proteins in the brains of living mice with Alzheimer’s disease. This study introduces a distinct design strategy for low-molecular-weight NIR-II dyes and addresses a longstanding bottleneck in this field.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Chi Zhang,Li Jun,Yuxiang Gao,Le Guo,Jiayi Ding,Lijun Zhu,Zhong Du,Jiabao Xiong,Xueliang Zhang,Wenbao Zhang,Biao Dong,Nuernisha Alifu
Alveolar echinococcosis (AE) is a serious parasitic infectious disease that is highly invasive and destructive to the liver and has a high mortality rate. However, currently, there is no effective targeted imaging and treatment method for the precise detection and therapy of AE. We proposed a new two-step targeting strategy (TSTS) for AE based on poly(lactic-co-glycolic acid) (PLGA). We designed and constructed a novel type of ICG@PLGA@Lips nanoprobe with integrated imaging and treatment properties. First, we used the characteristics of PLGA gluconeogenic raw material to target the liver during blood circulation. Then, we utilized the characteristics of PLGA specifically penetrating the AE shell to achieve specific identification of AE in the liver. Under 808 nm laser excitation, ICG@PLGA@Lips effectively achieved accurate imaging of AE based on near-infrared II (NIR-II, 900–1700 nm) fluorescence imaging methods and achieved AE treatment through PDT effects. PLGA improved the optical properties of ICG, while liposomes further improved the biocompatibility of the nanoprobe. As ICG@PLGA@Lips showed strong NIR-II fluorescence emission and good biocompatibility, ICG@PLGA@Lips showed advantages in the specific fluorescence navigation of AE surgical resection lesions. Thus, with the assistance of ICG@PLGA@Lips, we achieved precise targeted and real-time NIR-II fluorescence imaging of AE for the first time. We successfully obtained in vivo NIR-II fluorescence imaging-guided photodynamic/surgical therapy of AE. This TSTS-based AE imaging and treatment exploration provided a new strategy for accurate imaging and treatment of early AE, which is expected to significantly improve the prognosis of patients.
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ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xin Huang,Jiawei Zhu,Chuhuang Dong,Yuqing Li,Qing Yu,Xuan Wang,Zhejie Chen,Jiabei Li,Yu Yang,Haifang Wang
Ag2S quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of Ag2S QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag2+ and thus serve as a template to result in biomimetic mineralization and formation of pApt-Ag2S QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of Ag2S QDs, pApt-Ag2S QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of Ag2S QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both in vitro and in vivo.
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Materials Today Bio
·
2024
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IF 8.7
Xiaoqi Yang,Yuanyi Wang,Chunrong Qu,Boyu Tan,Minjin Wang,Senrui Li,Jinsheng Huang,Jiangnan Li,Mengyuan Fang,Zhen Cheng,Nan Zhou
Neuroanatomical tract tracers are important for studying axoplasmic transport and the complex interconnections of the nervous system. Though traditional fluorescent tracers are widely used, they have several prominent drawbacks when imaging, including low resolutions and low tissue penetrations and inability to be supervised dynamically within a long peripheral nerve during the long term. Here, we explored the potential of ICG as a neural tracer for axoplasmic transport and for the first time demonstrated that ICG could be used to detect transport function within peripheral nerve by near-infrared region II (NIR-II) imaging. On basis of this finding, a novel bi-directional neural tracer biotinylated dextran amine-indocyanine green (BDA-ICG) was prepared and characterized with better long-term stability and higher nerve-to-background ratio than ICG in vivo, and successfully imaged the injured peripheral nerve from the healthy one within 24 h. Our results show that BDA-ICG are promising neural tracers and clinically available dyes with NIR-II emission tail characteristics as ICG.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-14
·
IF 14.7
Wang Chenlu,Zhou Liping,Liu Chengzhe,Qiao Jiaming,Han Xinrui,Wang Luyang,Liu Yaxi,Xu Bi,Qiu Qinfang,Zhang Zizhuo,Wang Jiale,Zhou Xiaoya,Zeng Mengqi,Yu Lilei,Fu Lei
Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K + Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.
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Nature Protocols
·
2025
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IF 16
Yan Dingyuan,Li Xue,Wang Huanhuan,Li Bin,Wang Wei,Liao Yuhui,Tang Ben Zhong,Wang Dong
Phototheranostics, which allows simultaneous diagnosis and therapy, offers notable advantages in terms of noninvasiveness, controllability and negligible drug resistance, presenting a promising approach for disease treatment. By integrating second near-infrared (NIR-II, 1,000–1,700 nm) phototheranostic agents characterized by aggregation-induced emission (AIE) and cell membranes with specific targeting capacity, we have developed a versatile type of biomimetic nanoparticle (NP) for precise phototheranostics of pulmonary tuberculosis (TB). Coating the phototheranostic agents with preactivated macrophage membranes results in the formation of biomimetic NPs, which exhibit specific binding to TB through a lesion–pathogen dual-targeting strategy, allowing the accurate detection of Mycobacterium tuberculosis via NIR-II fluorescence imaging and precise photothermal therapy using the irradiation of a 1,064 nm laser. In comparison with traditional treatments, small individual granulomas (0.2 mm in diameter) in TB-infected mice are visualized, and improved antibacterial effects are achieved upon NP administration. Here we present a standardized workflow for the synthesis of the NIR-II AIE agents, their use for the fabrication of the biomimetic NPs and their in vitro and in vivo applications as phototheranostics against M. tuberculosis . The preparation and characterization of the NIR-II AIE agents requires ~8 d, the synthesis and characterization of the phototheranostic NPs requires ~8 d, the validation of in vitro targeting capacity and photothermal eradication requires ~26 d, and the in vivo NIR-II fluorescence imaging and imaging-guided photothermal therapy requires ~74 d. All procedures are straightforward and suitable for clinicians or researchers with prior training in organic synthesis and biomedical engineering.
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RSC Advances
·
2025
·Vol. 15
·期 15
·11893-11901
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IF 4.6
Xixi Wu,Xiang Feng,Peng Yu,Jing Zhang,Rui Liu
Breast cancer remains a significant global health concern owing to the limitations of conventional therapies, such as side effects, drug resistance, and high costs. Nanocatalytic therapy has emerged as a promising alternative due to its tumor specificity, spatiotemporal controllability, and noninvasiveness. However, its effectiveness is limited by endogenous antioxidants like glutathione (GSH) and the low catalytic activity of nanocatalysts. Herein, an Cu/Au-doped polypyrrole nanocatalyst, Cu-AuPP, with multiple catalytic activities is developed by sequentially polymerizing pyrrole monomers using CuCl2 and HAuCl4, followed by PEGylation. The obtained Cu-AuPP catalyzes the production of hydroxyl radicals (·OH) and facilitates the oxidation of GSH to GSSG via redox reactions mediated by multivalent Cu ions, leading to oxidative damage, mitochondrial dysfunction, and tumor cell apoptosis. Upon 1064 nm laser irradiation, these catalytic activities were enhanced by elevated temperature and electron–hole separation mediated by Au nanoclusters, resulting in more intense oxidative damage to tumor cells. Collectively, the developed Cu-AuPP nanocatalytic medicine capable of simultaneously catalyzing GSH depletion and ·OH production via several improved catalytic mechanisms, has significant promise for the treatment of malignant tumors.
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Small
·
2023
·Vol. 19
·期 19
·2300203
·
IF 13.3
Jun Guan,Chang Liu,Chendong Ji,Wenchao Zhang,Zongyang Fan,Penggang He,Qiuhong Ouyang,Meng Qin,Meizhen Yin
Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000–1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.
研究领域:
生物医学工程
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药学
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癌症研究
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纳米技术
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神经科学
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Theranostics
·
2019
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IF 8.063
Zhe Feng,Xiaoming Yu,Minxiao Jiang,Liang Zhu,Yi Zhang,Wei Yang,Wang Xi,Gonghui Li,Jun Qian
Rationale: Cerebrovascular diseases, together with malignancies, still pose a huge threat to human health nowadays. With the advantages of its high spatial resolution and large penetration depth, fluorescence bioimaging in the second near-infrared spectral region (NIR-II, 900-1700 nm) and its related imaging-guided therapy based on biocompatible fluorescence dyes have become a promising theranostics method. Methods: The biocompatibility of IR-820 we used in NIR-II fluorescence bioimaging was verified by long-term observation. The model of the mouse with a cranial window, the mouse model of middle cerebral artery occlusion (MCAO) and a subcutaneous xenograft mouse model of bladder tumor were established. NIR-II fluorescence cerebrovascular functional imaging was carried out by IR-820 assisted NIR-II fluorescence microscopy. Bladder tumor was treated by NIR-II fluorescence imaging-guided photothermal therapy. Results: We have found that IR-820 has considerable NIR-II fluorescence intensity, and shows increased brightness in serum than in water. Herein, we achieved real time and in vivo cerebrovascular functional imaging of mice with high spatial resolution and large penetration depth, based on IR-820 assisted NIR-II fluorescence microscopy. In addition, IR-820 was successfully employed for NIR-II fluorescence imaging and photothermal therapy of tumor in vivo , and the subcutaneous tumors were inhibited obviously or eradicated completely. Conclusion: Due to the considerable fluorescence intensity in NIR-II spectral region and the good photothermal effect, biocompatible and excretable IR-820 holds great potentials for functional angiography and cancer theranostics in clinical practice.
研究领域:
生物医学工程
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神经科学
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肿瘤学
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Small
·
2024
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IF 13
Muhammad Hassan,Yi Tan Su,Sania Zafar Iqbal,Raziq Nawaz,Yucai Wang,Wei Jiang
Near-infrared-II (NIR-II) fluorescence imaging-guided photothermal therapy (PTT) represents a cutting-edge approach for precise tumor diagnosis and treatment, providing real-time therapeutic efficacy evaluation. However, a significant challenge lies in the creation of phototheranostic agents that provide robust imaging and efficient photothermal conversion. To address this, a donor- π -acceptor (D- π -A) structure heptamethine cyanine derivative, IR1116, that confers a strong intramolecular charge transfer effect is developed. To enhance its applicability, IR1116 is formulated with DSPE-PEG to create a water-dispersible NIR-II phototheranostic nanoheater, NP IR1116 . This nanoheater benefits from the incorporation of an electron-withdrawing group, leading to reduced photooxidation activity and significantly improved photostability. NP IR1116 exhibits strong NIR-II absorption and fluorescence, peaking at 1004 and 1116 nm, respectively, as well as a photothermal conversion efficiency of 79% under 1064 nm lasers. In vitro and in vivo studies showed the efficacy of NP IR1116 in tumor imaging via NIR-II fluorescence and its ability to effectively induce tumor cell apoptosis under 1064 nm laser irradiation. These findings underscore the potential of NP IR1116 in NIR-II fluorescence imaging-guided PTT for tumor treatment, paving the way for further advancements in NIR-II dye development and bioimaging technologies.
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