Single-domain antibody C7b for address delivery of nanoparticles to HER2-positive cancers.
Single-domain antibody C7b for address delivery of nanoparticles to HER2-positive cancers.
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DOI：
10.1039/d0nr04899b
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发表时间：
2020-10
期刊：
影响因子：
6.7
通讯作者：
Yuri A. Vorotnikov;E. D. Novikova;A. Solovieva;D. Shanshin;A. Tsygankova;D. N. Shcherbakov;O. Efremova;M. Shestopalov
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文献类型：
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作者：
Yuri A. Vorotnikov;E. D. Novikova;A. Solovieva;D. Shanshin;A. Tsygankova;D. N. Shcherbakov;O. Efremova;M. Shestopalov
单抗在癌症等疾病的治疗以及多组分治疗或诊断系统的靶向递送方面显示出巨大的潜力。然而，单抗的物理尺寸大、稳定性差以及异常的过敏反应仍然是影响其广泛使用的主要问题。单域抗体(SdAb)被视为下一代抗体衍生疗法和诊断学。这项工作提出了HER2特异性sdAbC7b的优化生产方法，使∼的蛋白质产量提高了11倍。此外，对与C7b结合的模型纳米颗粒Cargo(掺有Mo6磷光团簇的50 nm二氧化硅颗粒)与与HER2特异的曲妥珠单抗结合的模型纳米颗粒Cargo的体外和体内效率进行了基准测试。具体地说，这篇论文证明了带有C7b的纳米颗粒在异种移植瘤组织中的积聚和排泄速度明显更高，这对诊断特别重要，即投放显像剂。
Monoclonal antibodies (mAb) demonstrate great potential as immunotherapy agents for the treatment of diseases such as cancer as well as tagging for the targeted delivery of multicomponent therapeutic or diagnostic systems. Nevertheless, the large physical size, poor stability of mAbs and abnormal allergic reactions still remain the main issues affecting their generalised use. Single-domain antibodies (sdAb) are seen as the next generation of antibody derived therapeutics and diagnostics. This work presents the optimised production method for HER2-specific sdAb C7b, which led to an ∼11-fold increase in protein yield. In addition, the in vitro and in vivo efficiencies of the targeted delivery of a model nanoparticle cargo (50 nm silica particles doped with Mo6 phosphorescent clusters) conjugated to C7b against those conjugated to HER2-specific trastuzumab is benchmarked. Specifically, this paper demonstrates the significantly higher rate of accumulation in and excretion from xenograft cancer tissue of nanoparticles with C7b, which is of particular importance for diagnostics, i.e. delivery of imaging agents.