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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-17 · IF 15.7

GCN5-targeted dual-modal probe across the blood-brain barrier for borders display in invasive glioblastoma

Zheng Haiyan,Zhang Lu,Bai Xinning,Zhu Jinchao,Liu Shanshan,Ke Yao,Lin Qingyuan,Yuan Yuan,Ji Tianhai

Glioblastoma (GBM) is a highly invasive malignancy with a poor prognosis, primarily attributable to its diffuse infiltration into adjacent brain tissue, thereby complicating effective surgical resection. Current imaging modalities often struggle to accurately identify tumor boundaries. Here, we identify general control non-repressed protein 5 (GCN5) as a promising molecular target for GBM imaging, as it is expressed in GBM lesions within brain tissue, and its expression levels are significantly correlated with GBM grading. We develop a dual-modal probe with a particle size of 20 nm, capable of efficiently traversing the blood-brain barrier (BBB) to target GCN5 through adsorptive-mediated transcytosis (AMT). The probe employs dendrimers (Den) as carriers, which are loaded with a small molecule inhibitor specifically designed to target GCN5. This probe enhances the preoperative delineation of GBM boundaries using magnetic resonance imaging (MRI) and facilitates intraoperative fluorescence image-guided surgical procedures. Our work introduces a promising tool for boundary delineation, offering new opportunities for the precise resection of GBM.

研究领域: 医学影像学 · 神经肿瘤学 · 分子生物学
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Materials Chemistry Frontiers · 2024 · IF 6

A hypochlorite-activatable persistent luminescence nanoprobe for assisted tumor resection

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
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Frontiers in Bioengineering and Biotechnology · 2020 · IF 3.644

Ultrasound Molecular Imaging as a Potential Non-invasive Diagnosis to Detect the Margin of Hepatocarcinoma via CSF-1R Targeting

Jiang Qiongchao,Zeng Yunting,Xu Yanni,Xiao Xiaoyun,Liu Hejun,Zhou Boyang,Kong Yao,Saw Phei Er,Luo Baoming

Though radiofrequency ablation (RFA) is considered to be an effective treatment for hepatocellular carcinoma (HCC), but more than 30% of patients may suffer insufficient RFA (IRFA), which can promote more aggressive of the residual tumor. One possible method to counter this is to accurately identify the margin of the HCC. Colony-stimulating factor 1 receptor (CSF-1R) has been found to be restrictively expressed by tumor associated macrophages (TAMs) and monocytes which more prefer to locate at the boundary of HCC. Using biotinylation method, we developed a CSF-1R-conjugated nanobubble CSF-1R (NBCSF–1R) using a thin-film hydration method for margin detection of HCC. CSF-1R expression was higher in macrophages than in HCC cell lines. Furthermore, immunofluorescence showed that CSF-1R were largely located in the margin of xenograft tumor and IFRA models. In vitro, NBCSF–1R was stable and provided a clear ultrasound image even after being stored for 6 months. In co-culture, NBCSF–1R adhered to macrophages significantly better than HCC cells (p = 0.05). In in vivo contrast-enhanced ultrasound imaging, the washout half-time of the NBCSF–1R was significantly greater than that of NBCTRL and Sonovue® (p = 0.05). The signal intensity of the tumor periphery was higher than the tumor center or non-tumor region after NBCSF–1R injection. Taken together, NBCSF–1R may potentially be used as a non-invasive diagnostic modality in the margin detection of HCC, thereby improving the efficiency of RFA. This platform may also serve as a complement method to detect residual HCC after RFA; and may also be used for targeted delivery of therapeutic drugs or genes.

CAS / MDL: 25322-68-3
研究领域: 医学影像 · 肿瘤学 · 生物医学工程 · 分子生物学
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Advanced Healthcare Materials · 2023 · IF 10

Tumor Microenvironment-Responsive Hydrogel for Direct Extracellular ATP Imaging-Guided Surgical Resection with Clear Boundaries

Jingyi Yang,Jiahao Qu,Xuanming Teng,Weiping Zhu,Yufang Xu,Yangyang Yang,Xuhong Qian

Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt-HEX/Cp-BHQ1 Gel, termed AHB Gel) is developed for fluorescence-guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP-responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100–500 µ m ) but shows little fluorescence at low ATP concentrations (10–100 n m ) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP-high and ATP-low regions. In vivo, AHB Gel exhibits specific tumor-targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment-targeted DNA-hybrid hydrogel for ATP-based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence-guided surgeries in the future.

CAS / MDL: 110-26-9 56-65-5
研究领域: 生物医学工程 · 癌症研究 · 材料科学 · 外科肿瘤学
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