JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Minlu Cheng,Xianjing Li,Ya Li,Yiya Wang,Wenjia Li,Shuai Wang,Chang Shu,Qinxin Song,Li Ding
Recently, the approval of Trop-2 targeted antibody drug conjugate (ADC) has changed the dilemma of patients with advanced triple-negative breast cancer who rely on chemotherapeutics to improve their survival. FDA018, an ADC consisting of an anti-Trop-2 antibody conjugated with a topoisomerase inhibitor SN-38 via an acid-cleavable linker, is currently being investigated in clinical trials. Based on the urgent demand to evaluate the clinical pharmacokinetics of FDA018, ligand binding assays (LBAs) for the determination of SN-38-conjugated antibody and total antibody and LC-MS/MS methods for the determination of the free SN-38, its metabolite SN-38G and total SN-38 were developed. The comparability and DAR sensitivity evaluation of the ELISA strategies for SN-38-conjugated antibody and total antibody were emphasized. The sensitivity of the LC-MS/MS method for the simultaneous determination of SN-38 and SN-38G reached 0.500 ng/mL and 0.250 ng/mL, respectively. An effective solution has been proposed for the optical instability of the cleavable linker of FDA018 during the pretreatment process of biological samples. The established bioanalytical methods were comprehensively validated and the results satisfied the acceptable criteria of ICH M10. The validated bioanalytical methods have been applied to the single-dose pharmacokinetic study of FDA018 in patients with Trop-2-positive malignant tumors successfully, and the pharmacokinetic profiles of FDA018 and its constituent components were investigated.
研究领域:
肿瘤学
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药物分析
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临床药理学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2023
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IF 8.4
Tianyu Zeng,Shuai Wu,Qizhi Liang,Hai Shi,Jue Gong,Ningjun Duan,Wei Li,Genxi Li,Yongmei Yin
The emergence of antibody-drug conjugates (ADCs) targeting trophoblast cell-surface antigen-2 (Trop-2) has reshaped the therapeutic landscape of advanced breast cancer. Accurate profiling of the Trop-2 status of tumor cells can facilitate the identification of patients who will benefit from Trop-2-targeting therapy; however limited analytical method has hindered this process. In this study, we have proposed a specific and sensitive biosensor for visual tracking of the Trop-2 status of breast cancer cells based on tetrahedral DNA nanostructure (TDN)-decorated Fe-based metal-organic framework nanoparticles (TDN-PCN-222 (Fe)). In the design, a dual-aptamer-assisted biomimetic capture strategy shows high capture efficiency while maintaining the viability and original phenotype of captured cells, ensuring the accurate profiling of the Trop-2 status. Meanwhile, by using the high intrinsic peroxidase activity and excellent targeting ability of Trop-2-specific aptamer-linked TDN-PCN-222 (Fe), specific detection of Trop-2-positive tumor cells can be achieved with a limit of detection (LOD) of 10 cells/mL, and the Trop-2 status of tumor cells can be visually tracked. Moreover, the proposed biosensor has been successfully used for tracking the Trop-2 status of tumor cells in breast cancer tissues, suggesting that our method has great promise for clinical applications.
研究领域:
生物技术
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癌症生物学
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纳米技术
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分子诊断
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产品关联
DOI
高影响因子
Biomaterials Advances
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2025
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IF 6
Meng Lan,Fansu Meng,Lanwen Gao,Anil K. Giri,Makiya Nishikawa,Kosuke Kusamori,Jaiwoo Lee,Mulazim Hussain Asim,Shumaila Arshad,Honghui Gu,Qi Li,Lina Yang,Zhong Chen,Zhenjiang Yang,Jiajia Qin,Yu Cai
Background Triple-negative breast cancer (TNBC) faces great challenges in clinical treatment, owing to the lack of specific therapeutic targets and easy metastasis. The natural component baicalin can effectively inhibit the growth and metastasis of TNBC; however, it has some limitations, such as poor targeting and side effects. Nano targeted delivery systems can improve drug efficacy by enhancing drug accumulation and controlling drug release. Objective Trop-2 transmembrane glycoprotein expression is high in TNBC cells, suggesting that it can serve as a specific active targeting molecular-modified nano drug delivery system for TNBC to overcome non-specific distribution. Based on the characteristics of high-concentration glutathione in the tumor microenvironment, redox-sensitive nano-prodrugs (Trop2-BA-ss-PPEP) have been designed to achieve intelligent slow control and release of drugs. Methods The chemical structure of the Trop2-BA-ss-PPEP, and its stability, reductive response to drug release behavior, and targeting ability in vitro were characterized. Cell experiments and a transplanted tumor model verified the anti-tumor effect and biosafety. Results Trop2-BA-ss-PPEP was stable in a physiological environment and rapidly released the drug under reducing conditions. The experiments showed that Trop2-BA-ss-PPEP significantly promoted cellular uptake, and drug accumulation and maintenance time at the tumor site were increased. It enhanced the inhibitory effect on metastasis in vivo and in vitro, and no obvious toxicity or side effects were observed. Conclusion Trop2-BA-ss-PPEP was successfully constructed. The targeting ability, microenvironment responsiveness, and anti-tumor metastatic effects of Trop2-BA-ss-PPEP provide a new strategy for TNBC therapy, which has good application and transformation potential.
研究领域:
药学
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纳米技术
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肿瘤学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2025
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IF 6
Wenqing Shao,Xiaoting Liu,Yi Zhou
Background Triple-negative breast cancer (TNBC) is strongly linked to overexpression of Trop-2, a transmembrane glycoprotein biomarker implicated in its aggressive behavior. For in situ imaging and quantification of this membrane protein, we developed a highly sensitive fluorescence aptasensor. Results Upon recognition of Trop-2 by its specific aptamer, hybridization chain reaction (HCR) was triggered for in situ imaging of cell-surface Trop-2. Concurrently, catalytic hairpin assembly (CHA) amplified fluorescence signals for quantitative Trop-2 detection. Successful cellular imaging and quantitative Trop-2 detection were achieved a linear response was observed from 0.001 μM to 0.1 μM, the limit of detection (LOD) was determined to be 0.0009 μM. Trop-2 surface density measurements revealed average amount per cell of: 6.0 × 10 6 molecules per cell (MDA-MB-468), 2.0 × 10 6 molecules per cell (MCF-7), 6.6 × 10 5 molecules per cell (MDA-MB-231), and 4.1 × 10 5 molecules per cell (HL-7702). Significance To our current knowledge, the work represents the first aptasensor enabling both in situ Trop-2 protein imaging and quantitative comparison across diverse cell types. The proposed method shows promise for tumor diagnosis and therapeutic evaluation.
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2021
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IF 4.769
Min Pei,Tingting Liu,Lu Ouyang,Jianhua Sun,Xiaojie Deng,Xiaomin Sun,Wei Wu,Peng Huang,Yi-Li Chen,Xiaorong Tan,Xiaoyue Liu,Peng Zhu,Yongzhen Liu,Deheng Wang,Junliang Wu,Qi Wang,Guifeng Wang,Likun Gong,Qiuping Qin,Chunhe Wang
Antibody-drug conjugates (ADCs) are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies. In this study, we report the generation of a monoclonal antibody against monomethyl auristatin E (MMAE) and the development, validation, and application of sensitive and high-throughput enzyme-linked immunosorbent assays (ELISA) to measure the concentrations of MMAE-conjugated ADCs and total antibodies (tAb, antibodies in ADC plus unconjugated antibodies) in cynomolgus monkey sera. These assays were successfully applied to in vitro plasma stability and pharmacokinetic (PK) studies of SMADC001, an MMAE-conjugated ADC against trophoblast cell surface antigen 2 (TROP-2). The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit, Lys (m-dPEG24)-Cit, and Val-Cit linkers. The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation between serum concentrations and the OD 450 values, with R 2 at 1.000, and the dynamic range was 0.3–35.0 ng/mL and 0.2–22.0 ng/mL, respectively; the intra- and inter-assay accuracy bias% ranged from −12.2% to −5.2%, precision ranged from −12.4% to −1.4%, and the relative standard deviation (RSD) was less than 6.6% and 8.7%, respectively. The total error was less than 20.4%. The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters, which suggested that these can be applied to quantify MMAE-conjugated ADCs, as well as in PK studies. Furthermore, these assays can be easily adopted for development of other similar immunoassays.
研究领域:
药理学
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免疫学
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生物化学
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药物开发
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DOI
PubMed
高影响因子
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