Advanced Science
·
2025
·
IF 14.1
Yueyang He,Jinyan Lin,Jingwen Bai,Xiao Shen,Kangliang Lou,Yuanyuan Zhu,Zishan Qiao,Weiling Chen,Yang Li,Xiaolong Liu,Guojun Zhang
Breast-conserving surgery (BCS) has become the standard care for early-stage breast cancer. The accurate assessment of tumor margins is urgently required for BCS because positive resection margins often lead to local recurrence. To address this clinical dilemma, a Hf(IV)-coordinated NIR-II fluorescence “turn-on” nanoprobe based on the clinically approved NIR-II fluorescent dye indocyanine green (ICG) for intraoperative tumor visualization is developed. Notably, the fluorescence of ICG can be efficiently quenched by Hf(IV) and subsequently recovered in vivo, showing a remarkable fluorescence “quenching-recovery-amplification” capacity. This nanoprobe can effectively accumulate in tumor sites, accurately identifying submillimeter-sized primary and residual tumors with high sensitivity. In addition, subcutaneous, muscle-infiltrating, and orthotopic breast cancer models are built to repeatedly prove that this ultrasensitive nanoprobe is feasible for precise imaging-guided surgery in breast cancer. Overall, this study constructs an activatable fluorescent nanoprobe for real-time intraoperative tumor margin visualization, holding promise for complete surgical resection and reduction of local recurrence.
研究领域:
肿瘤学
·
生物医学工程
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Haoran Xu,Zhuoyi Ye,Xin Gao,Yue Dai,Yang Luo,Zhihao Han,Yueqing Gu
Breast cancer, globally the most common cancer in women, presents significant challenges in treatment. Breast-conserving surgery (BCS), a less traumatic and painful alternative to radical mastectomy, not only preserves the breast’s appearance but also supports postsurgical functional recovery. However, accurately identifying tumors, precisely delineating margins, and thoroughly removing metastases remain complex surgical challenges, exacerbated by the limitations of current imaging techniques, including poor tumor uptake and low signal contrast. Addressing these challenges, our study developed a series of GnRHR-targeted probes (YQGN-n) for fluorescence imaging and surgical navigation of breast cancer through a drug repositioning strategy. Notably, YQGN-7, with its high cellular affinity (Kd of 217.8 nM), demonstrates exceptional selectivity and specificity for breast cancer tumors, surpassing traditional imaging agents like ICG in tumor uptake and pharmacokinetic properties. Furthermore, YQGN-7’s effectiveness in surgical navigation, both for primary breast tumors and metastases, highlights its potential as a revolutionary tool in BCS.
研究领域:
肿瘤学
·
医学影像学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Jiaxian Cai,Chen Lian,Zeyu Lu,Qian Shang,Li Wang,Zhihao Han,Yueqing Gu
Hepatocellular carcinoma (HCC) is a frequent malignancy that has a high death rate and a high rate of recurrence following surgery, owing to insufficient surgical resection. Furthermore, HCC is prone to peritoneal metastasis (HCC-PM), resulting in a significant number of tiny cancer lesions, making surgical removal more challenging. As a potential imaging target, FGFR4 is highly expressed in tumors, especially in HCC, but is less expressed in the normal liver. In this study, we used computational simulation approaches to develop peptide I0 derived from FGF19, a particular ligand of FGFR4, and labeled it with the NIRF dye, MPA, for HCC detection. In surgical navigation, the TBR was 9.31 ± 1.36 and 8.57 ± 1.15 in HepG2 in situ tumor and HCC-PM models, respectively, indicating considerable tumor uptake. As a result, peptide I0 is an excellent clinical diagnostic reagent for HCC, as well as a tool for surgically resecting HCC peritoneal metastases.
研究领域:
肿瘤学
·
医学影像学
·
外科肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Zichao Yan,Yifei Wang,Minghan Qiu,Kai Long,Zhouyu Zhang,Mengjie Sun,Chang Yin,Wei Wang,Huaqing Wang,Zhi Yuan
Surgical resection remains the main treatment for malignant tumors. Image-guided surgery aims to remove tumor tissue completely while preserving normal tissue, thereby reducing patient recurrence rates and injury. However, challenges like tissue autofluorescence, limited probe penetration and low contrast restrict its use. Near-infrared (NIR) persistent luminescent nanoparticles (PLNPs) provide a solution by emitting persistent luminescence (PersL) even after excitation ceases, thus circumventing autofluorescence and enabling deep tumor imaging. In this study, we prepared nano-sized (140-nm hydrodynamic size) Cr3+ doped zinc gallogermanate (ZGC) using a removable template method and modified it with folate acid to obtain ZGC-FA, which exhibits NIR (695 nm) PersL with a signal-to-noise ratio of 23.9 in vivo. We utilized colon cancer model that selectively expressing luciferase for the first time to validate the guiding efficacy of ZGC-FA in the precision surgical resection. Post-intraperitoneal injection at 50 minutes, the PersL closely matched the tumor boundaries, achieving an overlap rate of approximately 98%. Complete tumor resection was achieved under PersL guidance, with only 2.3% of healthy tissue removed. This research underscores the potential of ZGC-FA in the field of surgical oncology. The precision of the ZGC-FA guided surgical approach holds promise to enhance surgical outcomes and facilitate postoperative recovery for patients.
研究领域:
肿瘤学
·
医学影像
·
生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Lin Yuan,Yingbin Su,Runfeng Zhang,Jie Gao,Bing Yu,Hailin Cong,Youqing Shen
Organic small molecule fluorescent groups have injected new material support into the field of medical imaging due to their unique luminescence mechanism and easy tuning of structure. The great potential of NIR-II window imaging forces us to continuously optimize the structure of organic fluorophores to design better fluorescent molecules for fluorescence imaging-guided surgery. An ideal organic small molecule fluorescent group: it can penetrate into the inside of the organism, clearly present the internal structure and the edge contour of different tissues, so as to perfectly achieve internal imaging and accurately guide external surgery. In vivo, fluorescent groups do not damage normal tissues and organs. However, problems such as low quantum yield and poor biocompatibility greatly limit the clinical transformation of NIR-II fluorescent small molecules. To avoid the shortcomings of NIR-II fluorescent probes as much as possible and better realize image-guided surgery, in this experiment, the biplane donor unit was incorporated into the twisted D-π-A-π-D structure to expand the conjugated structure of the fluorescent group, which not only realized NIR-II emission, but also had high quantum yield and biosafety.
研究领域:
生物医学工程
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2024
·
IF 6
Zhouyu Zhang,Zi-Jin Wei,Mengjie Sun,Zichao Yan,Chang Yin,Wei Wang,Zhi Yuan
Surgical resection is widely recognized as one of the most effective treatments for cancer. However, it requires precise and convenient visualization of tumor boundaries to assist surgeons. Persistent luminescence nanoparticles (PLNPs) exhibit bright and long-lasting afterglow, non-autofluorescence interference, and excellent photostability, making them ideal candidates for surgical navigation. Nevertheless, the currently used persistent luminescence tumor imaging method suffers from the issue of ambiguous tumor boundaries. Hence, a hypochlorite-responsive near-infrared (NIR) absorber A690 was bonded to ZnGa2O4:Cr3+ (ZGC) PLNPs coated with DSPE-mPEG2000 (ZGC@P&A). In normal tissue, ZGC@P&A was quenched due to the Förster resonance energy transfer from ZGC PLNPs to A690 molecules. Upon uptake by cancer cells, ZGC@P&A was turned “on” through the oxidation of A690 by high levels of hypochlorite. Compared to non-responsive ZGC@P, ZGC@P&A not only effectively eliminated interference from peripheral normal tissue afterglow but also accurately aligned with the tumor boundary within 30 minutes of peritumoral injection. Under the guidance of ZGC@P&A, the tumor was completely excised with minimal removal of surrounding tissue. Hypochlorite-activatable PLNPs greatly enhance the credibility of imaging, opening up new perspectives for a variety of clinical diagnostic applications.
研究领域:
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 15
·3317-3325
·
IF 6.331
Lixiu Chen,Bin Xia,Bing Yan,Jianhua Liu,Zhaohua Miao,Yan Ma,Jinchen Wang,Hu Peng,Tao He,Zhengbao Zha
Multifunctional contrast-enhanced agents suitable for application in surgical navigation by taking advantage of the merits of their diverse imaging modalities at different surgical stages are highly sought-after. Herein, an amphipathic polymer composed of aggregation-induced emission fluorogens (AIEgens) and Gd3+ chelates was successfully synthesized and assembled into ultrasound responsive microbubbles (AIE-Gd MBs) to realize potential tri-modal contrast-enhanced ultrasound (US) imaging, magnetic resonance imaging (MRI), and AIEgen-based fluorescence imaging (FI) during the perioperative period. Through ultrasound targeted microbubble destruction (UTMD) and cavitation effect, the as-prepared AIE-Gd MBs went through a MBs-to-nanoparticles (NPs) conversion, which not only resulted in targeted accumulation in tumor tissues but also led to stronger fluorescence being exhibited due to the more aggregated AIE-Gd molecules in the NPs. As a proof-of-concept, our work proposes a strategy of US-lit-up AIEgens in tumors which could offer a simple and powerful tool for surgical navigation in the future.
研究领域:
医学影像学
·
生物材料学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-12
·
IF 4.703
Huang Xin,Chen Qian,Li Xin,Lin Chenyu,Wang Kun,Luo Cici,Le Wenjun,Pi Xiaodong,Liu Zhongmin,Chen Bingdi
At present, various fluorescent nanomaterials have been designed and synthesized as optical contrast agents for surgical navigation. However, there have been no reports on the preparation of fluorescent contrast agents for lung cancer surgery navigation using silicon quantum dots (Si QDs). This study improved and modified the water-dispersible Si QD micelles reported by Pi et al. to prepare Si QD micelles-CKAP4. The data showed that the Si QD micelles-CKAP4 were spherical particles with a mean hydrodiameter of approximately 78.8 nm. UV–visible absorption of the Si QD micelles-CKAP4 ranged from 200 to 500 nm. With an excitation wavelength of 330 nm, strong fluorescence at 640 nm was observed in the fluorescence emission spectra. Laser confocal microscopy and fluorescence microscopy assay showed that the Si QD micelles-CKAP4 exhibited good targeting ability to lung cancer cells and lung cancer tissues in vitro. The in vivo fluorescence-imaging assay showed that the Si QD micelles-CKAP4 was metabolized by the liver and excreted by the kidney. In addition, Si QD micelles-CKAP4 specifically targeted lung cancer tissue in vivo compared with healthy lung tissue. Cytotoxicity and hematoxylin and eosin staining assays showed that the Si QD micelles-CKAP4 exhibited high biosafety in vitro and in vivo. Si QD micelles-CKAP4 is a specifically targeted imaging agent for lung cancer and is expected to be a fluorescent contrast agent for lung cancer surgical navigation in the future.
研究领域:
纳米技术
·
癌症研究
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生物医学工程
·
光学成像
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2023
·
IF 4.7
Song Jian,Ren Tingting,Duan Yanheng,Guo Haitao,Wang Gang,Gan Yu,Bai Mengcai,Dong Xiaotian,Zhao Zheng,An Jiaze
Background: Near-infrared fluorescence (NIRF) imaging has recently emerged as a promising tool for noninvasive cancer imaging. However, lack of tumor sensitivity and specificity restricts the application of NIRF dyes in surgical navigation.Methods: Herein, we investigated the imaging features of NIRF dye MHI-148 and indocyanine green (ICG) in live cell imaging and xenograft nude mice models. TCGA dataset analysis and immunohistochemistry were conducted to investigate the expression of OATPs or ABCGs in hepatocellular carcinoma (HCC) tissues. OATPs or ABCGs were knocked down and overexpressed in HCC cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Further, qRT-PCR ,Western blotting and the use of agonists or inhibitors targeting β-catenin signaling pathway were applied to explore its important role in regulation of OATP2B1 and ABCG2 expression.Results: Here we demonstrated that NIRF dye MHI-148 was biocompatible as indocyanine green (ICG) but with higher imaging intensity and preferential uptake and retention in hepatocellular carcinoma (HCC) cells and tissues. Moreover, our data indicated that membrane transporters OATP2B1 and ABCG2, which regulated by β-catenin signaling pathway, mediated tumor-specific accumulation and retention of MHI-148 in HCC cells. In addition, the treatment with β-catenin inhibitor significantly enhanced the accumulation of MHI-148 in HCC tissues and improved the efficacy of tumor imaging with MHI-148 in vivo.Conclusions: Our study uncovers a mechanism that links the distribution and expression of the membrane transporters OATP2B1 and ABCG2 to the tumor-specific accumulation of MHI-148, and provides evidence supporting a regulating role of the β-catenin signaling pathway in OATP2B1 and ABCG2- induced retention of MHI-148 inHCC tissues, and strategy targeting key components of MHI-148 transport machinery may be a potential approach to improve HCC imaging.
研究领域:
癌症生物学
·
分子生物学
·
医学成像
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
·
2021
·Vol. 49
·期 3
·847-860
·
IF 9.236
Liu Jing-Jing,Wang Zun,Nie Li-Ming,Zhu Yuan-Yuan,Li Ge,Lin Lin-Ling,Chen Min,Zhang Guo-Jun
Purpose Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. Methods The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. Results The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. Conclusion These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.
研究领域:
医学影像
·
癌症手术
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Jian Sun,Jintao Ye,Wenwei Tang,Bin Yu,Yong Gao,Shengli Wang,Haijuan Zhang
Surgical precision in tumor resection critically relies on real-time intraoperative imaging, yet conventional probes face limitations in specificity and spatiotemporal control. Here, we present a tumor microenvironment (TME)-activated near-infrared (NIR) fluorescent nanoprobe (DNS–DYE/PEG–NI) that integrates dual responsiveness to hypoxia and glutathione (GSH) for submillimeter-level surgical navigation. The system comprises a GSH-activatable NIR fluorophore (λex/em = 679/730 nm) quenched by 2,4-dinitrobenzenesulfonyl (DNS) moieties and hypoxia-sensitive amphiphilic PEG–NI micelles. Upon tumor accumulation via the enhanced permeability and retention (EPR) effect, a hypoxic TME triggers micelle disassembly through nitroimidazole (NI) reduction, releasing DNS–DYE. Subsequent GSH cleavage restores fluorescence via intramolecular charge transfer (ICT) recovery, achieving a 12.3-fold tumor-to-normal tissue signal ratio and >90% reduction in off-target activation compared to non-responsive controls. Systematic validation demonstrates: (1) dose-dependent fluorescence recovery (35-fold intensity increase at 10 mM GSH); (2) hypoxia-driven micelle destabilization (800% hydrodynamic diameter expansion); (3) sustained colloidal stability (12.9% size variation over 15 days); and (4) low cytotoxicity (cell viability >90% at 125 μg mL−1). In vivo studies reveal precise tumor delineation within 12 h post-injection, enabling real-time resection of submillimeter lesions. By coupling TME-specific activation with prolonged tumor retention, this dual-responsive nanoprobe advances fluorescence-guided surgery toward precision oncology, reducing positive margin rates from 70% to <5% in preclinical models.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
分子成像
·
外科肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）