JOURNAL OF MEDICINAL CHEMISTRY
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2025
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IF 6.8
Hao Tian,Quan Zuo,Siqi Zhang,Hongyi Huang,Dengfu Wu,Zihan Huang,Xiangding Liu,Lin Xie,Yiding Zhang,Hailong Zhang,Yekuan Shi,Suping Li,Ming-Rong Zhang,Rui Wang,Kuan Hu
The development of ideal peptide-based radiopharmaceuticals faces critical bottlenecks, primarily due to limited cellular internalization and insufficient deep tissue penetration of peptide carriers. To address this, we developed an intracellular targeting and DNA-adjacent radiotherapeutic strategy using stapled peptides. The MDM2/MDMX-targeting stapled peptide-based radiopharmaceuticals, denoted as [64Cu]Cu-DOTA-STP, exhibited prolonged circulation in the bloodstream and slow systemic clearance. Furthermore, in vitro studies demonstrated that nearly 50% of administered [64Cu]Cu-DOTA-STP was internalized, achieving efficient intracellular accumulation. In addition, [64Cu]Cu-DOTA-STP demonstrated high tumor accumulation, with a standard uptake value of up to 9.39 ± 1.52%ID/g. Finally, targeted radionuclide therapy confirmed that [64Cu]Cu-DOTA-STP effectively inhibited tumor growth, irrespective of p53 phenotypes. Taken together, this study leveraged PET imaging as a noninvasive and longitudinal tool to elucidate the in vivo fate of stapled peptides and demonstrated that stapled peptides can serve as ideal vehicles for developing intracellular protein-targeting radiopharmaceuticals, achieving efficient 64Cu-based targeted radionuclide therapy.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Jie Zhong,Shuang Yan,Yanling Yu,Guihao Hu,Wei Chen,Haiyu Wang,Wenxue Li,Jinping Yuan,Suping Li,Xinghui Li,Xiaoming Zhang,Changqiang Wu
Radiolabeled superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention for their potential in dual-modality imaging, combining positron emission tomography (PET) and magnetic resonance imaging (MRI). The integration provides clinicians with enhanced and complementary imaging information, improving the accuracy of disease diagnosis. However, the complexity of ligand synthesis for functionalization and stable radiolabeling and the difficulty in achieving controlled large-scale production with consistent nanoparticle quality, both of which limit their potential in clinical applications. To overcome these limitations, we report a novel method for preparing SPIONs utilized a simple dual-chelation functional ligand and a continuous synthesis approach to facilitate their clinical translation. The functionalized SPIONs were successfully synthesized by using a flow synthesis technique and the dual-chelation functional ligand (PAsp- g -DA/EA). Compared with traditional synthesis methods, this approach enabled mass production with high reproducibility. The obtained SPIONs showed ultra-small sizes (5.1 ± 0.1 nm), good monodispersity, excellent relaxivity, and superior biocompatibility. The dual-chelation functional ligand enabled direct and efficient radiolabeling of SPIONs with [ 64 Cu]Cu 2+ achieving over 80 % efficiency and outstanding labeling stability. After intravenous injection into rats, high-quality PET and MRI images were obtained. Furthermore, both PET and MRI demonstrated significant nanoprobe accumulation in tumor-bearing mice. In this study, a dual-chelation functional ligand was employed to facilitate the batch and reproducible synthesis of directly radiolabelable SPIONs, thereby addressing key challenges associated with the clinical translation of PET/MRI dual-modality nanoprobes. The nano-probes developed demonstrate excellent biocompatibility, superior imaging efficacy in both PET and MRI, making them potential candidates for medical PET/MRI dual-modality probes.
研究领域:
医学影像学
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纳米医学
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放射化学
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DOI
高影响因子
Frontiers in Oncology
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2021
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IF 6.244
Wen Li,Xia Lei,Guo Xiaoyi,Huang Hai-Feng,Wang Feng,Yang Xian-teng,Yang Zhi,Zhu Hua
Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.
研究领域:
肿瘤学
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分子影像
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纳米医学
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癌症治疗
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DOI
PubMed
高影响因子
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