Previous studies have shown the potential of bevacizumab-based ADCs in tumor vascular normalization and chemotherapy synergies. Here, in order to improve the tumor treatment efficiency of ADC and further avoid drug resistance, we introduced the previously discovered photodynamic therapy group PDT into bevacizumab, which has high reactive oxygen generation efficiency and deep tissue penetration ability, and has surprising imaging effect on solid tumors. At the same time, doxorubicin, a chemotherapy drug molecule with strong cytotoxicity, has also been introduced to construct novel multifunctional integrated antibody-drug conjugates, Bevacizumab-DOX-PDT. It is proved that novel ADCs have the antigen-antibody binding ability similar to bevacizumab, while also possess strong antitumor activity and vascular normalization activity. In addition, it also showed great tracer ability for transplanted tumors. In summary, the novel ADC showed a surprising vascular normalization-chemotherapy-photodynamic synergistic therapeutic effect, which further enriched the expansion of vascular normalization in the field of new drug discovery.
Bioconjugate chemistry. 2025 Apr 8. doi: 10.1021/acs.bioconjchem.5c00116 Q14.02024
Discovery of a Novel ADC for Multifunctional Theranostics: From Vascular Normalization to Synergistic Therapy
用于诊疗一体化的新型多功能抗体偶联药物发现:从血管正常化到协同治疗 翻译改进
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DOI: 10.1021/acs.bioconjchem.5c00116 PMID: 40197042
摘要 中英对照阅读
先前的研究已经证明了基于贝伐单抗的抗体药物偶联物(ADC)在肿瘤血管正常化和化疗协同作用方面的潜力。在这里,为了提高ADC的肿瘤治疗效率并进一步避免耐药性问题,我们将之前发现的光动力疗法组PDT引入到贝伐单抗中。这种光动力疗法具有高效的活性氧生成能力和深层组织穿透能力,并且对实体瘤有惊人的成像效果。同时,我们还将强细胞毒性的化疗药物多柔比星(Doxorubicin)分子引入进来,构建了一种新型多功能集成抗体-药物偶联物——Bevacizumab-DOX-PDT。证明这种新的ADC具有与贝伐单抗相似的抗原抗体结合能力,并且还具备强大的抗肿瘤活性和血管正常化活性。此外,它在移植瘤中的示踪能力也非常出色。总之,该新型ADC展示了令人惊讶的血管正常化、化疗和光动力协同治疗效果,这进一步丰富了新药发现领域中血管正常化的扩展范围。
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