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CD20
Journal of Nanomaterials · 2018 · IF 2.207

Identification on Mantle Cell Lymphoma Using CD20 and CD5 Coupled Upconversion Fluorescent Nanoprobes

Mingkai Zhang,Yang Gao,Jialiang Wang,Zhanbo Liu,Zaishun Jin,Jianbo Yu,Yukuan Feng,Qiang Lü

In order to determine a particular tumor cell via nanomaterials, we introduce the preparation of CD20 and CD5 coupled nanoprobes (denoted as CD20 and CD5 nanoprobes for convenience) and an application in identification of mantle cell lymphoma (MCL) from B-cell lymphoma. In this work, CD20 and CD5 nanoprobes were prepared by selectively oxidizing the carbon-carbon double bonds of oleate ligands on the surfaces of NaYF4:Yb3+,Tm3+ and NaYF4:Yb3+,Er3+ nanoparticles and, respectively, coupling carboxyl groups on the particles’ surfaces with CD20 and CD5 monoclonal antibodies through EDC/NHS crosslinking agents. After in situ hybridized Jeko-1 cells and Raji cells as a reference with CD20 and CD5 nanoprobes, in vitro double-color upconversion fluorescence imaging of Jeko-1 cells was demonstrated through visualization of blue and green fluorescence under a 980 nm laser excitation. Moreover, in vivo upconversion fluorescence imaging of the transplanted cancer model was also measured. These experimental results indicate that Jeko-1 cells have been specifically labeled by CD20 and CD5 nanoprobes. It is therefore concluded that CD20 and CD5 nanoprobes could be used to specially differentiate mantle cell lymphoma (MCL) from B-cell lymphoma.

研究领域: 生物医学工程 · 癌症研究 · 纳米技术 · 免疫学
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Materials Today Bio · 2025 · IF 10.2

CD20 targeted nanomedicine for GCB-diffuse large B-cell lymphoma through synergistic effects of apoptosis and ferroptosis

Shu-xian Liu,Jun-yu Zhang,Xiao-yan Zheng,Yong-zhong Du,Xiang-min Tong

Diffuse large B-cell lymphoma (DLBCL) is one of the most prevalent lymphomas, and can be classified as activated B-cell DLBCL (ABC-DLBCL) or germinal center B-cell DLBCL (GCB-DLBCL) according to molecular subtypes. Studies have shown that drug resistance is an important factor in its therapeutic failure. Tumor-specific drug delivery nanocarriers may be a promising strategy for the treatment of lymphoma. Herein, we developed a nanomedicine (RTX-DOX/DMF-Lip, RDDL) carrying the chemotherapeutic drugs doxorubicin (DOX) and dimethyl fumarate (DMF), and surface-modified with rituximab (RTX), which can recognize CD20 antigen when it comes into contact with the surface of a B-lymphoma cell. In the study, we found that DOX and DMF can be delivered to the tumor site precisely and demonstrate a potent synergistic anti-tumor effect. Once the nanomedicine was internalized, it induced apoptosis through ROS generation and the activation of caspase-3. Concurrently, DMF directly reduced the levels of glutathione (GSH) in tumor cells by inhibiting System Xc - , thereby resulting in impaired ROS detoxification and fostering an environment conducive to lipid peroxidation (LPO) and ferroptosis. Furthermore, the ROS generated by DOX synergistically propelled the process of ferroptosis, creating a potent therapeutic effect. These effects were validated in the GCB-DLBCL mouse model, where RDDL had a more potent killing effect compared to free drugs by striking SU-DHL-10 cells through a dual mechanism of apoptosis and ferroptosis, providing a new therapeutic strategy for the treatment of drug-resistant GCB-DLBCL.

研究领域: 肿瘤学 · 药理学 · 纳米医学
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Journal of Materials Chemistry B · 2019 ·Vol. 8 ·期 5 ·895-907 · IF 5.047

Rituximab conjugated iron oxide nanoparticles for targeted imaging and enhanced treatment against CD20-positive lymphoma

Lina Song,Yi Chen,Jiali Ding,Haoan Wu,Wei Zhang,Ming Ma,Fengchao Zang,Zhongqiu Wang,Ning Gu,Yu Zhang

Since its launch in 1997, rituximab (RTX) has extensively improved the treatment of CD20-positive follicular and diffuse large B cell non-Hodgkin lymphoma (NHL). The application of RTX is limited usually by the failed therapy because of resistance. Iron oxide nanomaterials have been explored for cancer detection and treatment in recent years. In this study, a multivalent nanoprobe comprising one Fe3O4 nanoparticle and several RTX antibodies was constructed for the targeted imaging and enhanced treatment of NHL. Poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles were fabricated via a thermal decomposition method and ligand exchange. RTX was conjugated onto the surface of the Fe3O4-PEG nanoparticles to form Fe3O4-PEG-nAb (n = 2, 5 or 8) multivalent nanoprobes. These multivalent nanoprobes, with a core size of approximately 11 nm and a hydrodynamic diameter of about 22 nm, showed colloidal stability in buffer solution. The r2 relaxation rate of Fe3O4-PEG-nAb was similar to that of Fe3O4-PEG (309 ± 3.08 mM−1 s−1). The specificity of nanoprobes for CD20-positive Raji cells was assessed on a clinical magnetic resonance imaging scanner. The receptor binding site of one multivalent nanoprobe was more than that of one RTX, exhibiting valence-dependent induction of Raji cell apoptosis, and this effect could be enhanced by complement activation from blood serum added. A similar activity was observed in vivo in a NHL xenograft model. The multivalent nanoprobe treatment significantly reduced tumor burden and enhanced survival in comparison to the RTX group. Our studies demonstrate that the appropriate design and preparation of anticancer antibody–nanoparticle conjugates enable the generation of improved anticancer nanomedicines and could thus provide an efficient cancer theranostic strategy.

研究领域: 肿瘤学 · 纳米医学 · 分子影像 · 癌症治疗
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BIOSENSORS & BIOELECTRONICS · 2020 · IF 10.257

Anti-fouling poly adenine coating combined with highly specific CD20 epitope mimetic peptide for rituximab detection in clinical patients’ plasma

Shengfeng Huang,Rentao Tang,Tingting Zhang,Jing Zhao,Zhengjin Jiang,Qiqin Wang

In this study, a high-performance anti-fouling coating based on poly adenine (polyA n ) as well as a highly specific cluster of differentiation 20 (CD20) epitope mimetic peptide (CN14) were employed to synergistically construct a facile biosensor for the rapid and sensitive determination of rituximab in lymphoma patients' plasma. The well-designed and optimized polyA n coating displayed excellent stability, hydrophilicity , thanks to its intrinsic affinity with gold surface and thoroughly exposed hydrophilic phosphate groups. Moreover, the proposed strategy avoids the necessity to modify binding groups (e.g. thiol), making it more facile, repeatable and efficient. When dealing with complex clinical plasma samples, the polyA n coating demonstrated better anti-fouling performance and lower background signal in comparison with mercaptan and bovine serum albumin coatings. The dissociation constant (~60 nM) between CN14 and rituximab was measured by microscale thermophoresis and their binding mechanism was further explained using computer simulation. The constructed GE/CN14/polyA 20 biosensor displayed satisfactory performance with detection limit of 35.26 ng/mL. Finally, the proposed biosensor was successfully applied for rapidly determining rituximab in lymphoma patients' plasma, and exhibited comparable accuracy to the commercial ELISA , but has advantages including a shorter detection time, wider detection range and lower cost. It's worth noting that the anti-fouling polyA n coating can be tailored according to the surface property of sensing interface and can be easily expanded to other gold electrode related biosensors.

研究领域: 生物医学工程 · 临床化学 · 生物传感器 · 癌症研究
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Oncotarget · 2017 · IF 5.168

Application of a double-colour upconversion nanofluorescent probe for targeted imaging of mantle cell lymphoma

Guang Yang,Yong Cao,Bin Yan,Qiang Lv,Jianbo Yu,Fusheng Zhao,Zhihong Chen,Heran Yang,Mengxi Chen,Zaishun Jin

Upconversion nanoparticles are a new type of fluorescent marker in biomedical imaging that can convert a longer wavelength (such as near-infrared fluorescence) into a shorter wavelength (such as visible light). Mantle cell lymphoma, which is derived from B-cell lymphoma, is a subtype of non-Hodgkin's lymphoma, and the immune phenotype is a mature B-cell phenotype (CD20+, CD5+). To develop the use of nanomaterials as specific markers for the medical imaging of mantle cell lymphoma, we modified the surface of UCNPs by oxidation so that the CD20 or CD5 antibody could covalently attach to the upconversion nanoparticles to form antibody-UCNP conjugates. These antibody-UCNP conjugates were used as fluorescent probes to detect the CD20 or CD5 antigen. Due to the excessive expression of these antigens on the surface of MCL cells and successful strong connection between the antibody and UCNPs, the latter could specifically combine with mantle cell lymphoma cells. Upon near-infrared excitation at 980 nm, cells labelled with UCNPs emitted bright upconversion fluorescence.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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CHEMICAL ENGINEERING JOURNAL · 2021 · IF 13.273

Multifunctional DNA mediated spatially confined assembly for antibody orientation: Surpassing sensitivity and accuracy for rituximab detection

Shengfeng Huang,Weida Wang,Jiamin Li,Tingting Zhang,Yang Liang,Qiqin Wang,Zhengjin Jiang

The sensitive, accurate and fast monitoring of therapeutic drugs plays an important role in guiding clinical medication or individualized treatment. Inspired by the highly efficient interactions of ordered structures in living organisms, a multifunctional DNA mediated spatially confined assembly (SCA) based antibody orientation strategy was proposed in this work. The multifunctional DNA containing a signaling molecule labeled on the head and a poly adenine tail (20 bases), can not only direct the ordered immobilization of antibodies on gold nanoparticles, but can also enrich electrochemical signal molecules. Compared with a randomly arranged antibody immobilization strategy, the SCA based antibody orientation strategy can produce nearly 200% of peak current signal. Moreover, MoS 2 /gold nanoparticles were used to modify electrodes in this study in order to improve the electrochemically active surface area and electron transfer of the electrode as well as the spatial regulation of thiol peptides. By using a highly specific CD20 epitope mimetic peptide this proposed biosensor exhibits high sensitivity for rituximab detection (LOD 56.4 fM) as well as good selectivity, stability and satisfactory accuracy. When applying it for detecting rituximab in lymphoma patients’ plasma, comparable results to commercial ELISA were obtained with a low RSD (<6.5%). The proposed signal tag fabrication strategy could easily be extended to analyze other targets by changing the sensing platform, which has a potential application in the fields of biological analysis and medical diagnosis.

研究领域: 生物传感器 · 纳米技术 · 电化学 · 药物监测 · 医学诊断
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