JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2025
·
IF 1.6
Li Yuan-Yuan,Yu Jia-Yan,Wang Tao,Wang Jing,Zhao Peng,Yang Xia,Wei Hong-Yuan,Chen Yue
Fab fragments obtained via enzymatic digestion of full-length antibodies or by gene recombination technology have smaller molecular weight and greater penetration ability. Those advantages make it uniquely suited to deliver radionuclides. In this study, we prepared a Fab fragment from the anti-EGFR antibody Cetuximab and labeled it with 177 Lu. The binding activity in vitro and biodistribution in vivo of [ 177 Lu]Lu-DOTA-Fab-Cetuximab were investigated. The [ 177 Lu]Lu-labeled Fab fragment showed improved tumor penetration and faster blood clearance compared to the full-length antibody.
研究领域:
医学
·
肿瘤学
·
核医学
✓ 已验证
产品关联
DOI
高影响因子
PLoS One
·
2017
·Vol. 12
·期 1
·e0170013
·
IF 2.806
Sheng Liu,Wenjie Gao,Yao Wang,Zhenyu He,Xiaojun Feng,Bi-Feng Liu,Xin Liu
Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness.
研究领域:
生物制药
·
蛋白质组学
·
药物分析
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Bin Li,Zhongyin Jiang,Diya Xie,Yiqing Wang,Xingzhen Lao
Background Photothermal therapy (PTT) has received extensive attention owing to its non-invasive nature and highly therapeutic outcomes. PTT agents and near-infrared (NIR) laser are essential elements in PTT. However, most PTT agents are composed of heavy metals, characterized by serious cytotoxicity and side effects, and NIR irradiation often damages normal tissue owing to the high dose, thus limiting the clinical application of PTT. Purpose In this regard, exploring new perspectives enabling more PTT agents to be enriched into the tumor and NIR laser irradiation decay in PTT is vital. Methods In this study, cetuximab (Ab), an anti-angiogenic antibody which targets the EGFR, was modified on CuS NPs (CuS-Ab NPs) to improve the aggregation of CuS NPs in the tumor. Results The cellular uptake data and the biodistribution results showed comparable accumulation of CuS-Ab NPs in tumor, thus decreasing the cytotoxicity and side effects in normal tissues. More importantly, the modification of Ab in CuS-Ab NPs impressively inhibited the formation and progression of tumor vessels, as demonstrated by immunohistochemistry staining. The introduction of anti-vessel treatment requires CuS-Ab NPs to provide weak PTT, which means that a small amount of laser energy is required, inevitably causing negligible damage to normal tissue. Conclusion Therefore, our tailor-made CuS-Ab NPs have promising potential in clinical applications.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2023
·Vol. 332
·期 6
·2093-2102
·
IF 1.6
Li Kehong,Fan Wenqi,Yan Jingxuan,Wang Jing,Zhao Peng,Liao Wei,Yang Yuchuan,Yang Xia,Wei Hongyuan,Chen Yue
Differences in cellular radiosensitivity and the binding affinity of radiopharmaceuticals could directly affect the radiotherapeutic effects. In this study, we investigated the radionuclide ( 177 Lu) induced radiosensitivity of serval non-small-cell lung cancer cells (NSCLCs) as well as the binding affinity of cetuximab to those cells. The apoptosis of NSCLCs caused by 177 Lu was related to the DNA double-strand damage and was cell-type dependent. We also proved that the introduction of 177 Lu to the antibody could enhance its cytotoxic effect on NSCLCs. The [ 177 Lu]Lu-DOTA-cetuximab could accumulate in the HCC827 tumor xenografts with excellent stability according to in vivo SPECT/CT imaging and the biodistribution results. The [ 177 Lu]Lu-DOTA-cetuximab showed high potential to be used for targeting diagnosis and radiotherapy in lung cancers.
研究领域:
肿瘤学
·
放射生物学
·
核医学
✓ 已验证
产品关联
DOI
高影响因子
Materials Express
·
2021
·Vol. 11
·期 10
·1619-1627
·
IF 0
Zhang Yue,Liu Yuanfen,Hu Yumin,Pan Lei
In this study, we developed an active targeting nano-immunoplatform of doxorubicin (DOX)-loaded bovine serum albumin (BSA) modified with the humanized antibody cetuximab, which can target the epidermal growth factor receptor (EGFR) of EGFR-overexpressing colon cancer, and subjected
it to a series of in vitro evaluation. The obtained cetuximab-modified nanoparticles (cetuximab-DOX-immuno-NPs) had an average particle size of 218.2±2.2 nm, a polydispersity index of 0.162±0.023, a zeta potential of −23.28±0.75 mV, and a cetuximabloading
efficiency of 33.6%±3.5%. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity experiments showed that the cytotoxic of cetuximab-DOX-immuno-NPs in EGFR-overexpressing RKO colon cancer cells was significantly higher than it was in EGFR-under-expressing
LS174 T cells. The results of flow cytometry showed that when DOX-immuno-NPs were used, DOX was eliminated soon after entering the cells, whereas when cetuximab-DOX-immuno-NPs were used, DOX efflux was reduced. Confocal laser-scanning microscopy was used to visualize the endocytosis of nanoparticles,
and revealed that the fluorescence intensity of cetuximab-DOX-immuno-NPs was significantly higher than that of non-specific IgG-DOX-immuno-NPs in RKO cells. Moreover, in EGFR-under-expressing LS174 T cells, both cetuximab-DOXimmuno-NPs and Immunoglobulin G-DOX-immuno-NPs showed weak DOX fluorescence
intensity, reflecting the specificity and selectivity of cetuximab-modified nanoparticles toward EGFR-overexpressing cancer cells. This study demonstrated that cetuximab modification of DOX-loaded BSA nanoparticles can increase their selectivity and reduce their toxicity. As this would decrease
the side effects of these treatments in patients, this study shows that cetuximab-modified doxorubicin-loaded bovine serum albumin nanoparticles are promising candidates for targeted colon cancer therapy.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
International Journal of Nanomedicine
·
2023
·
IF 8
Buyankhishig Dorjsuren,Birendra Chaurasiya,Zixuan Ye,Yanyan Liu,Wei Li,Chaoyang Wang,Di Shi,Colin E Evans,Thomas J Webster,Yan Shen
Background One major limitation of cancer chemotherapy is a failure to specifically target a tumor, potentially leading to side effects such as systemic cytotoxicity. In this case, we have generated a cancer cell-targeting nanoparticle-liposome drug delivery system that can be activated by near-infrared laser light to enable local photo-thermal therapy and the release of chemotherapeutic agents, which could achieve combined therapeutic efficiency.Methods To exploit the magnetic potential of iron oxide, we prepared and characterized citric acid-coated iron oxide magnetic nanoparticles (CMNPs) and encapsulated them into thermo-sensitive liposomes (TSLs). The chemotherapeutic drug, doxorubicin (DOX), was then loaded into the CMNP-TSLs, which were coated with an antibody against the epidermal growth factor receptor (EGFR), cetuximab (CET), to target EGFR-expressing breast cancer cells in vitro and in vivo studies in mouse model.Results The resulting CET-DOX-CMNP–TSLs were stable with an average diameter of approximately 120 nm. First, the uptake of TSLs into breast cancer cells increased by the addition of the CET coating. Next, the viability of breast cancer cells treated with CET-CMNP-TSLs and CET-DOX-CMNP-TSLs was reduced by the addition of photo-thermal therapy using near-infrared (NIR) laser irradiation. What is more, the viability of breast cancer cells treated with CMNP-TSLs plus NIR was reduced by the addition of DOX to the CMNP-TSLs. Finally, photo-thermal therapy studies on tumor-bearing mice subjected to NIR laser irradiation showed that treatment with CMNP-TSLs or CET-CMNP-TSLs led to an increase in tumor surface temperature to 44.7°C and 48.7°C, respectively, compared with saline-treated mice body temperature ie, 35.2°C. Further, the hemolysis study shows that these nanocarriers are safe for systemic delivery.Conclusion Our studies revealed that a combined therapy of photo-thermal therapy and targeted chemotherapy in thermo-sensitive nano-carriers represents a promising therapeutic strategy against breast cancer.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
生物医学工程
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Xi-Ling Li,Chengqiang Han,Miao Luo,Shuyun Xiao,Jing Li,Chenglong Yu,Shengyu Cheng,Yueying Jin,Yu Han,Kenichiro Todoroki,Qing Shi,Jun Zhe Min
Glycans play important roles in the activity and function of monoclonal antibodies (mAbs). In this study, an isotope labeling method for the relative quantitative analysis of glycans in cetuximab, a chimeric human/mouse IgG1 monoclonal antibody that specifically targets epidermal growth factor receptor, via hydrophilic interaction LC-ultra-high-performance LC-HRMS was established based on Pronase E digestion. To this aim, novel isotope MS probes, i.e., 3-benzoyl-2-oxothiazolidine-4-carboxylic acid (d0-BOTC) and 3-(2,3,4,5,6-pentadeuterio-benzoyl)-2-oxothiazolidine-4-carboxylate acid (d5-BOTC), which include a carboxyl group to target the amino functional group in glycosylamine, were developed. The nonspecific Pronase E enzyme could simultaneously digest the peptide bound to the N - and O -glycans into glycosylamine having only one amino acid. Since the mass difference between the light- and heavy-labeled glycans was 5.0 Da, the relative abundance of their MS peaks was used to achieve the qualitative and relative quantitative analysis of glycans. Sialylglycopeptide was used as a complex glycan model to validate the accuracy of the method. The results demonstrated the good linearity (R 2 ≥ 0.9994) between the experimentally detected MS intensity ratios and the theoretical molar ratios of the d0-BOTC to the corresponding d5-BOTC derivatives in the dynamic range of 0.03-10 and 0.03-20 of three orders magnitude for the d5-BOTC/d0-BOTC ratios. The reproducibility was between 0.16% and 10.70%, and the limit of detection was 13 fmol. The feasibility of the relative quantification method was investigated by analyzing the glycan content in cetuximab, finding good consistency between experimental and theoretical molar ratios (5:1, 3:1, 1:1, 1:3, 1:5) of d0/d5-BOTC-labeled glycans. Finally, 13 glycans were successfully identified in cetuximab by applying this method using an in-house Tracefinder database. This study provides a novel strategy for the high throughput analysis, identification, and functional study of glycans in mAbs.
研究领域:
生物化学
·
药物分析
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Gastrointestinal Oncology
·
2021
·
IF 2.892
Linghui Kong,Qun Zhang,Jialei Mao,Lei Cheng,Xiao Shi,Lixia Yu,Jing Hu,Mi Yang,Li Li,Baorui Liu,Xiaoping Qian
Background Epidermal growth factor receptor (EGFR) and its downstream Ras-mitogen-activated protein kinase kinase (MAPKK, MEK)-extracellular regulated protein kinase (ERK) signaling pathway and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway play important roles in the pathogenesis of colorectal cancer (CRC). The combination therapy of anti-EGFR and anti-mTOR needs to be explored. Methods Here we combined the anti-EGFR monoclonal antibody cetuximab (CTX) with the mTOR inhibitor PP242 in CRC cell lines and mouse xenograft models and discussed the changes of EGFR downstream signaling pathways of CRC cell lines. Results In HT-29 cells and Caco-2 cells, combined application of CTX and PP242 significantly inhibited the proliferation of CRC cells in vivo and in vitro. In BRAF wild-type Caco-2 cells, combined application of CTX and PP242 inhibited the activation of the EGFR and its downstream signaling pathways. Conclusions Our research further demonstrates the effectiveness of the combined application of CTX and PP242 in inhibiting CRC cell lines from the perspective of cell proliferation, cell cycle, apoptosis, and mouse xenografts. We revealed that the combined application of CTX and PP242 can inhibit tumor growth and proliferation by inhibiting the phosphorylation of key molecules in EGFR downstream MEK-ERK and MEK 4/7 (MKK)-c-Jun N-terminal kinase (JNK) signaling pathways in BRAF wild-type CRC cells. In addition, we found that in BRAF mutant CRC cells, the monotherapy of PP242 resulted in negative feedback increased EGFR phosphorylation rates, accompanied by significant up-regulation of downstream MEK and ERK phosphorylation.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Xiaoyan Lu,Sha Liu,Meishan Han,Xiucheng Yang,Kaoxiang Sun,Hongbo Wang,Hongjie Mu,Yuan Du,Aiping Wang,Ling Ni,Chunyan Zhang
Afatinib , a selective and irreversible inhibitor of tyrosine kinase , was approved for the treatment of advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) overexpression in 2013. Cetuximab (CTX), an anti-EGFR monoclonal antibody , is co-administered with afatinib to improve efficacy. Unfortunately, dose-related adverse reactions caused by combination therapy have affected patient compliance, and have resulted in treatment discontinuation in severe cases. In the present study, afatinib was encapsulated in “liposomes” (LPs) to achieve longer circulation in the blood and an enhanced permeability-and-retention effect in tumors. Concomitantly, CTX was designed to bind to drug-loaded LPs to form “immuno-LPs” for tumor-cell selectivity and therapeutic activity. In vitro , the cellular internalization rate of immuno-LPs was significantly higher than that of LPs (p < 0.05). In vivo , a markedly increased area under the curve and prolonged terminal half-life were detected in rats injected with the two LP formulations, indicating that LP encapsulation protected afatinib from binding to hemoglobin to control the risk of idiosyncratic drug reactions . Compared with free afatinib and LPs, immuno-LPs exhibited strongly enhanced drug delivery and antitumor efficacy in an NSCLC xenograft model, with stronger tumor selectivity and potentially fewer side-effects. Hence, EGFR-targeting immuno-LPs appear to be promising for NSCLC treatment.
研究领域:
肿瘤学
·
药学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Liyin Wang,Milad Ashrafizadeh,Gautam Sethi,Xinjia Zhou
Suboptimal treatment of laryngeal squamous cell carcinoma (LSCC) reduces survival rate. The poor bioavailability and resistance to cetuximab (Cet) and the instability of small interfering RNA (siRNA) limit their therapeutic efficacy in LSCC. This study aimed to develop a Cet and focal adhesion kinase (FAK) siRNA (siFAK) co-delivery nanosystem. Zeolitic imidazolate framework-8 (ZIF-8), with its large specific surface area and pH-responsive properties, is an ideal delivery carrier that allows controlled drug release in the acidic tumor microenvironment. Therefore, Cet was loaded onto ZIF-8 and encapsulated in a TU177 cell membrane (TCM) after the electrostatic adsorption of siFAK. Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential, X-ray diffraction, and particle size analyses were used to characterize Cet/siFAK@ZIF-8@TCM. TU177 cells and subcutaneously transplanted tumor-bearing nude mice were used to evaluate the intracellular uptake, cytotoxicity, in vivo biocompatibility, biodistribution, biosafety, pH responsiveness, and anti-LSCC efficacy of Cet/siFAK@ZIF-8@TCM. After ZIF-8@TCM were loaded with Cet and siFAK, alterations in their physical and crystal structures, particle size, and zeta potential were observed. Meanwhile, the co-delivery system increased the loading of Cet through the electrostatic adsorption of siFAK to Cet-loaded ZIF-8. The intracellular uptake of Cet/siFAK@ZIF-8@TCM also protected siFAK from degradation, effectively reducing the messenger RNA (mRNA) and protein expression levels of FAK in LSCC cells. The ZIF-8@TCM nanosystem for co-delivery of Cet and siFAK exhibited pH-responsiveness and tumor-targeting capabilities, thereby exerting anti-LSCC effects. Co-delivery of Cet and siFAK via the pH-responsive ZIF-8@TCM system enabled the targeted release of the chemotherapeutic and gene, in turn maximizing their anti-LSCC effect while ensuring biosafety.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2021
·Vol. 9
·期 6
·2279-2294
·
IF 6.843
Ranran Chen,Yuanjian Huang,Lu Wang,Jiahui Zhou,Yuqian Tan,Chaofan Peng,Peng Yang,Wen Peng,Jie Li,Qiou Gu,Yuchen Sheng,Yan Wang,Guoqiang Shao,Qing Zhang,Yueming Sun
Antibody-functionalized targeted nanocarriers to deliver chemotherapeutics have been widely explored. However, it remains highly desirable to understand and apply the antitumor potential of antibodies integrated in hybrid composite nanoplatforms. Herein, mesoporous silica nanoparticles, a supported lipid bilayer and cetuximab were integrated to fabricate a hybrid nanoplatform for effectively encapsulating and selectively delivering 5-fluorouracil (5-FU) against colorectal cancer (CRC) cells. The specially designed nanoplatform exhibited superior properties, such as satisfying size distribution, dispersity and stability, drug encapsulation, controlled release, and cellular uptake. Interestingly, the modification of cetuximab onto nanoplatforms without drug loading can significantly inhibit the migration and invasion of CRC cells through suppressing the epidermal growth factor receptor (EGFR)-associated signaling pathway. Furthermore, delivery of 5-FU by using this nanoplatform can remarkably induce cytotoxicity, cell cycle arrest, and cell apoptosis for CRC cells with high EGFR expression. Overall, this nanostructured platform can dramatically improve the tumor killing effects of encapsulated chemotherapeutics and present antimigration effects derived from the antibody modified on it. Moreover, in vivo biodistribution experiments demonstrated the superior tumor targeting ability of the targeted nanoparticles. Thus, this targeted nanoplatform has substantial potential in combinational therapy of antibodies and chemotherapy agents against colorectal cancer.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
生物医学工程
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yurong Xiang,Qiang Liu,Kang Liu,Liuxian Chen,Fengjiao Chen,Tao Li,Siqi Li,Qiang Yu,Quan Lv,Zheng Xiang
Multi-drug combination therapy is one of the most effective strategies for the treatment of drug-resistant and advanced tumors. Modern nanodrug delivery systems are crucial for multi-drug combination therapy and gene therapy. However, research on direct injection of RNAi has not yielded significant results. Artificial vectors are emerging as promising delivery systemts for RNA for gene therapy. In this study, a multi-drug therapy system was built based on a biodegradable exosome nano-platform exploiting the protective and low immunogenic properties of exosomes for RNA. This work aimed to accomplish the co-delivery of siRNA and 3-Bromopyruvic acid (3BP) on an exosome nanoplatform, enhancing targeting by coupling cetuximab (CTX) to exosome membranes, resulting in a new nanomedicine Exo@siRNA/3BP-CTX (ERBC) engineered exosomes. The synthesis conditions were optimized to obtain stable, safe, and effective nanomedicines. Successful targeting of tumors with CTX inhibited KRAS oncogene expression and significantly reduced glucose uptake by cancer cells. This enhanced the starvation therapy effect of the energy deprivation agent 3BP, thus promoting excessive autophagy activation in cells and doubling apoptosis. However, ERBC combined with CTX therapy restored cellular chemosensitivity to CTX. These findings indicate that engineered exosomes with dual therapeutic activities is a promising approach for treating refractory KRAS-mutant cancers.
研究领域:
肿瘤学
·
基因治疗
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）