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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

Self-assembled multifunctional nanotheranostics loading GEM for targeted lung cancer therapy

Jun Tang,Fushuang Zheng,Jungang Zhao,Jianzhu Zhao

The aim of this study was to prepare a promising drug carrier for treatment of lung cancer. The self-assembly nanoparticles of SDP-GEM/PEI-PEG-anti-EGFR with chemotherapeutic drug of gemcitabine (GEM), Magnetic resonance imaging (MRI) guided- imaging and targeting of anti- Epidermal Growth Factor Receptor (anti-EGFR) were designed. The imaging capacity, targeting feasibility and anti-tumor function were evaluated respectively. SDP-GEM/PEI-PEG-anti-EGFR exhibited contrast enhancement under T2 Weight Image (T2WI) and a liner relationship was found between the concentration and relaxation rate of R2 and R2* in vitro . With the targeting of anti-EGFR, the endocytosis of nanoparticles increased significantly, which effectively killed lung cancer cells in vitro , and importantly it can be accurately delivered to tumor site within 3 h in vivo . Prolonged lifetime and smaller tumor volume demonstrated that SDP-GEM/PEI-PEG-anti-EGFR efficiently inhibited tumor growth in vivo . Therefore, SDP-GEM/PEI-PEG-anti-EGFR was an effective and safe drug carrier, which had a great potential application in MRI-guided lung cancer therapy.

研究领域: 纳米技术 · 癌症治疗 · 分子影像 · 药物递送系统
✓ 已验证 DOI PubMed 高影响因子
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ANALYTICAL BIOCHEMISTRY · 2015 · IF 2.219

Predicting the right spacing between protein immobilization sites on self-assembled monolayers to optimize ligand binding

Javier Batista Perez,Deependra Tyagi,Mo Yang,Loany Calvo,Rolando Perez,Ernesto Moreno,Jinsong Zhu

Self-assembled monolayers designed to immobilize capture antibodies are usually prepared using a mixture of functional and inactive linkers. Here, using low molar ratios (1:1 to 1:100) of the two linkers resulted in loss of binding capability of the anti-EGFR (epidermal growth factor receptor) antibody nimotuzumab, as assessed by surface plasmon resonance imaging. We then developed a simple theoretical model to predict the optimal surface density of the functional linker, taking into account the antibody size and linker diameter. A high (1:1000) dilution of the functional linker yielded the best results. As an advantage, this approach does not require chemical modification of the protein.

研究领域: 生物化学 · 分子生物学 · 生物物理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

UVA-responsive Fe₃O₄@ZnO nanocarrier grafted with anti-EGFR antibody for precision delivery of Nrf2-siRNA and brusatol: A novel platform for integrated photodynamic, gene, and chemotherapy

Qian Ren,Tingting Tian,Bin Wang,Jun Pan,Yong Huang,Li Zhong,Yehong Wang,Xia Wang,Xiao Huang

Photodynamic therapy (PDT) remains underutilized as a primary cancer treatment due to the limited lethality of reactive oxygen species (ROS) and poor targeting efficiency of traditional photosensitizers. This the aim of the study is to develop a Fe₃O₄@ZnO nanoparticle photosensitizer co-loaded with anti-EGFR antibody, brusatol, and Nrf2-siRNA to improve the therapeutic effect of PDT. This system can be guided to tumors by a magnetic field and further targets cancer cells through EGFR-specific binding. Under UVA light, brusatol and Nrf2-siRNA are released, enabling combined chemo-, gene, and photodynamic therapy. With the photosensitizer treatment, ROS levels in cutaneous squamous cell carcinoma cells were elevated by 191.09 ± 10.02 % through suppression of Nrf2 and its associated antioxidant defenses, significantly enhancing cell lethality and reducing cell viability by 80.43 ± 9.37 %. In vivo studies further demonstrated a tumor suppression rate of 76.30 ± 5.12 % in nude mice, highlighting the robust anti-tumor efficacy of the photosensitizer and its potential for clinical application in targeted cancer therapy. The biocompatibility and high therapeutic efficacy of this photosensitizer highlight its promise as a safer and more effective option for treating cutaneous squamous cell carcinoma.

CAS / MDL: 93642-68-3
研究领域: 癌症治疗 · 纳米技术 · 药理学 · 分子生物学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULAR THERAPY · 2024 · IF 12.1

In situ blockade of TNF-TNFR2 axis via oncolytic adenovirus improves antitumor efficacy in solid tumors

Xiaozhen Kang,Yifeng Han,Mengdi Wu,Yuxin Li,Peng Qian,Chuning Xu,Zhengyun Zou,Jie Dong,Jiwu Wei

Tumor necrosis factor (TNF) has been recognized as an immune activation factor in tumor immunotherapy. Our study demonstrated that TNF blockade markedly enhanced the antitumor efficacy of oncolytic adenovirus (AdV) therapy. To minimize systemic side effects, we engineered a recombinant oncolytic AdV encoding a TNF inhibitor (AdV-TNFi) to confine TNF blockade within the tumor microenvironment (TME). AdV-TNFi significantly improved therapeutic outcomes across various solid tumor models, including four murine and two golden hamster cancers. Immune cell profiling identified CD8 + T cells as the primary mediators of AdV-TNFi-induced antitumor effects, rather than CD4 + T or NK cells. Additionally, AdV-TNFi significantly decreased the infiltration of suppressive myeloid-derived immune cells within the TME and promoted long-term antitumor immune surveillance. Further investigation indicated that TNFR2, more than TNFR1, is pertinent to the immunosuppressive TME, with a recombinant AdV-encoding anti-TNFR2 demonstrating comparable antitumor efficacy to AdV-TNFi. Moreover, AdV-TNFi enhanced the antitumor efficacy of gemcitabine and immune checkpoint blockades (ICBs), such as anti-PD-L1 and anti-TIGIT antibodies, in pancreatic carcinoma and the anti-EGFR antibody in colon carcinoma. In conclusion, intratumoral blockade of the TNF/TNFR2 axis using AdV augments cancer immunotherapy efficacy while mitigating the risks associated with systemic TNF or TNFR2 suppression, warranting further clinical investigation.

研究领域: 肿瘤学 · 免疫学 · 分子生物学 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2018 ·Vol. 6 ·期 7 ·1011-1017 · IF 4.776

Transglutaminase mediated PEGylation of nanobodies for targeted nano-drug delivery

Tiantian Wu,Hai Huang,Yaping Sheng,Hongdong Shi,Yuanzeng Min,Yangzhong Liu

Targeted delivery of anticancer drugs that selectively accumulate in malignant cells could enhance drug efficacy and reduce side effects of conventional chemotherapy. In this work, we designed a single domain antibody (nanobody) based drug delivery system for targeted delivery of anticancer drugs. An anti-EGFR nanobody (Nb) was constructed with a C3-tag and a Q-tag for site specific modifications under physiological conditions. The site specific PEGylation of the nanobody was achieved via a transglutaminase catalyzed reaction through the coupling of the Q-tag with PEG-NH2. As a proof of concept, the PEGylated nanobody was tethered to HSA coated upconversion nanoparticles (UCNPs) through the C3-tag, and an anticancer drug, doxorubicin (DOX), was loaded. Results showed that the Nb-conjugated drug delivery system exhibits superior specificity to the EGFR positive tumor cells. The drug delivery system is highly accumulated in the EGFR positive tumor cells (A431), whereas there was no detectable accumulation in the EGFR negative cells (MCF-7). Consequently, the drug loaded particles demonstrated significantly higher anti-proliferation to A431 cells than to MCF-7 cells. This work provides an effective approach for site-specific modification of nanobodies for the construction of targeted drug delivery systems.

研究领域: 药学 · 纳米技术 · 癌症研究 · 生物技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TALANTA · 2021 · IF 6.057

Dual signal amplification based on polysaccharide-initiated ring-opening polymerization and click polymerization for exosomes detection

Xin Zhu,Zenghui Liu,Jinge Li,Zutian Li,Fuchun Si,Huaixia Yang,Jinming Kong

Exosomes, as a biomarker with enhancing tumor invasion and spread, play an essential role for lung cancer diagnosis, therapy, and prognosis. In this work, a novel electrochemical sensor was fabricated for detecting exosomes secreted by lung cancer cells based on polysaccharide-initiated ring-opening polymerization (ROP) and click polymerization. First, MPA formed a self-assembled monolayer on the gold electrode surface, and then anti-EGFR was immobilized on the electrode surface by amide bond. Subsequently, a lot of phosphate groups were introduced by the specific recognition between anti-EGFR and exosomes, then sodium alginate grafted Glycidyl propargyl ether (SA- g -GPE) prepared via ROP was attached to the exosomes through PO 4 3- Zr 4+ -COOH coordination bond. After that, click polymerization was initiated by alkyne groups on the SA- g -GPE polymerization chain to realize highly sensitive detection of A549 exosomes. Under the optimum conditions, the fabricated sensor showed a good linear relationship between the logarithm of exosomes concentration and peak current in the range of 5 × 10 3 - 5 × 10 9 particles/mL, and the limit of detection (LOD) was as low as 1.49 × 10 2 particles/mL. In addition, this method had the advantages of high specificity, anti-interference, high sensitivity, simplicity, rapidity and green economy, which proposed a novel avenue for the detection of exosomes, and also had potential applications in early cancer diagnosis and biomedicine.

研究领域: 生物标志物研究 · 癌症诊断 · 电化学 · 聚合物科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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