Trop2抗体与黑磷纳米片定向偶联用于原位胃癌光疗

IF 4.7 4区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Nanomedicine: Nanotechnology, Biology and Medicine Pub Date : 2023-07-01 DOI:10.1016/j.nano.2023.102687
Lizhou Jia PhD , Yuhao Fu MSc , Ning Zhang MB , Yang Liu MB , Lin Su MSc , Haisheng Wang PhD , Wei Zhao PhD
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引用次数: 0

摘要

肿瘤相关钙信号传感器2 (Trop2)在胃癌(GC)中高度特异性表达。Trop2抗体与光疗药物联合使用具有协同抗肿瘤活性。黑磷纳米片(BP)通过聚乙二醇(PEG)异双功能连接体与Trop2 IgG抗体共价修饰。然后通过氧化后的Trop2抗体的醛基与PEG的氨基之间的希夫碱反应,将Trop2抗体定向偶联至BP。在近红外(NIR)照射下,trop2功能化的BP可显著增加trop2阳性GC细胞的BP内吞,显示出增强的抗肿瘤活性。更重要的是,小鼠原位GC模型表明,Trop2抗体修饰可以显著促进BP在肿瘤组织的积累,增强光疗的抗肿瘤活性。Trop2抗体与BP定向偶联,使BP在近红外照射下具有优异的稳定性、肿瘤靶向能力和抗肿瘤活性,且无全身毒性。
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Directional conjugation of Trop2 antibody to black phosphorus nanosheets for phototherapy in orthotopic gastric carcinoma

Tumor-associated calcium signal transducer 2 (Trop2) is highly specific expressed in gastric carcinoma (GC). The combination of Trop2 antibody and phototherapy agents could exhibit synergetic antitumor activity. Black phosphorus nanosheets (BP) are covalently modified with Trop2 IgG antibodies via heterobifunctional linker of polyethylene glycol (PEG). Then the Trop2 antibody was directionally conjugated to BP via Schiff base reaction between aldehyde group from oxidized Trop2 antibody and amino group of PEG. The Trop2-functionalzied BP can significantly increase the endocytosis of BP in Trop2-positive GC cells exhibiting a reinforced antitumor activity under near infrared (NIR) irradiation. More importantly, a murine orthotopic GC model demonstrates that Trop2 antibody modification can significantly promote the accumulation of BP at tumor tissues and strengthen antitumoral activity of phototherapy. Directional conjugation of Trop2 antibody to BP facilitates the BP with superior stability, tumor targeting ability and excellent anti-tumor activity under NIR irradiation without systemic toxicity.

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来源期刊
CiteScore
8.10
自引率
3.60%
发文量
104
审稿时长
4.6 months
期刊介绍: Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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