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GPC-3
NANOTECHNOLOGY · 2021 ·Vol. 32 ·期 17 ·175101 · IF 3.874

A novel multifunctional gold nanorod-mediated and tumor-targeted gene silencing of GPC-3 synergizes photothermal therapy for liver cancer

Yanling Liu,Manman Tan,Chunjuan Fang,Xiaoyan Chen,Huan Liu,Ying Feng,Yujuan Zhang,Weiping Min

Tumor-specific targeted delivery is a major obstacle to clinical treatment of hepatocellular carcinoma (HCC). Here we have developed a novel multi-functional nanostructure GAL-GNR-siGPC-3, which consists of Galactose (GAL) as the HCC-targeting moiety, golden nanorods (GNR) as a framework to destroy tumor cells under laser irradiation, and siRNA of Glypican-3 (siGPC-3) which induce specifically gene silence of GPC-3 in HCC. Glypican-3 (GPC-3) gene is highly associated with HCC and is a new potential target for HCC therapy. On the other hand, Gal can specifically bind to the asialoglycoprotein receptor which is highly expressed on membrane of hepatoma cells. GAL and siGPC-3 can induce targeted silencing of GPC-3 gene in hepatoma cells. In vivo and in vitro results showed that GAL-GNR-siGPC-3 could significantly induce downregulation of GPC-3 gene and inhibit the progression of HCC. More notably, GAL-GNR-siGPC-3 could induce both GPC-3 gene silencing and photothermal effects, and the synergistic treatment of tumors was more effective than individual treatments. In summary, GAL-GNR-siGPC-3 achieved a synergistic outcome to the treatment of cancer, which opens up a new approach for the development of clinical therapies for HCC.

研究领域: 纳米技术 · 癌症治疗 · 分子生物学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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Nature Communications · 2026 · IF 18.1

Generation of GPC-3-targeted radicals for precise therapy of hepatocellular carcinoma

Hao Wanting,Zhang Meng,Fu Zi,Cui Xinyuan,Jiang Hongjing,Li Ruokun,Yan Fuhua,Ni Dalong

Exogenous free radicals oxidize and damage tumor proteins, but their non-specific reactivity also causes unintended harm to tumor-suppressive proteins, which compromises the therapeutic efficacy. Here we show a nanosystem that generates in-situ radical-conjugated species with predefined targeting capability toward oncogenic protein. This nanosystem consists of lipid nanoparticles encapsulating polyphenolic tannic acid and hydrophobic calcium peroxide nanoparticles in spatially segregated compartments. Upon cellular uptake, the components are released into the cellular membrane through membrane fusion. Consequently, calcium peroxide nanoparticles act as oxidizing agents, radicalizing tannic acid, which generates gallic acid species conjugated with phenoxyl radicals. Since gallic acid confers specific binding affinity for the oncogenic GPC-3 protein in hepatocellular carcinoma, the radical-conjugated species integrate dual functionalities: a targeting module that binds to the oncogenic GPC-3 protein, and a stabilized phenoxyl radical inducing site-specific oxidative damage. These species direct to GPC-3 and induce localized disruption of critical peptide segments and lipid domains, triggering protein cleavage and membrane shedding, which suppresses downstream signaling including the canonical Wnt/β-catenin pathway and finally inhibits hepatocellular carcinoma progression. By enabling site-specific radical delivery, this strategy achieves precise inactivation of predefined oncogenic targets and establishes a framework for molecularly free-radical-mediated antitumor therapy.

✓ 已验证 DOI 高影响因子
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TALANTA · 2025 · IF 6.1

Dual-antibody functionalized transistor biosensor for specific diagnosis of liver cancer

Yi Yu,Wenhao Zhang,Qiyue Ding,Xiaolu Cheng,Kaiwei Wang,Guangxin Zhang,Boan Jiang,Xionghua Yu,Yu-Tao Li,Guo-Jun Zhang

Selectively and sensitively detecting specific exosomal markers is critical for early diagnosis of liver cancer. However, identifying specific exosomal biomarkers and establishing accurate, convenient detection methods remain challenging. In this study, we used bioinformatics to identify the higher levels of EpCAM and GPC-3 proteins on liver cancer exosomes. These markers were used to create a dual-antibody functionalized transistor biosensor for precise detection of liver cancer exosomes. The techniques exhibited outstanding specificity and sensitivity. Detection thresholds in PBS and simulated plasma were established at 20 particles/μL and 47 particles/μL, respectively, facilitating the distinction of liver cancer cell-derived exosomes from those originating from various other cancer cells. Furthermore, in clinical samples testing, this approach not only distinguished clinical samples among liver cancer patients and healthy individuals, but also demonstrated the ability to differentiate liver cancer from other types of tumors, achieving a precision and accuracy rate of 100 %. The developed biosensor demonstrates excellent potential for clinical application and this work offers a promising and effective approach for cancer diagnosis.

CAS / MDL: 97427-71-9
研究领域: 医学诊断 · 生物信息学 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF NANOBIOTECHNOLOGY · 2022 ·Vol. 20 ·期 1 ·1-20 · IF 9.429

Targeted-detection and sequential-treatment of small hepatocellular carcinoma in the complex liver environment by GPC-3-targeted nanoparticles

Deng Han,Shang Wenting,Wang Kun,Guo Kunxiong,Liu Yu,Tian Jie,Fang Chihua

Despite advancements in diagnostic methods and therapeutic strategies, the mortality rate of hepatocellular carcinoma (HCC) remains as high as its incidence rate. Most liver cancers are detected in the advanced stages, when treatment options are limited. Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment, especially in cirrhotic livers. In the present study, we developed a tumor “cruise missile”, mesoporous Fe 3 O 4 -containing glucose oxidase-conjugated GPC3 peptide nanoparticles (FGP NPs). It was designed to enhance the accuracy of small HCC visualization to 85.7% using combined ultrasound/photoacoustic imaging in complex liver environment, which facilitated sequential catalytic targeted therapy for small HCC. In a carcinogen-induced mouse HCC model, FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules, such as cirrhosis nodules and necrotic nodules, by dynamic contrast-enhanced photoacoustic imaging. In a mouse xenograft HCC model, highly reactive oxygen species were formed by sequential catalytic reactions, which promoted HCC cell apoptosis, significantly increasing the survival of the model mice. The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment. Graphical Abstract

研究领域: 癌症生物学 · 纳米技术 · 医学成像 · 治疗学
✓ 已验证 DOI PubMed 高影响因子
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