Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Bioconjug Chem. 2022 May 18;33(5):969-981. doi: 10.1021/acs.bioconjchem.2c00167. Epub 2022 May 6.
Lipid-based formulations provide a nanotechnology platform that is widely used in a variety of biomedical applications because it has several advantageous properties including biocompatibility, reduced toxicity, relative ease of surface modifications, and the possibility for efficient loading of drugs, biologics, and nanoparticles. A combination of lipid-based formulations with magnetic nanoparticles such as iron oxide was shown to be highly advantageous in a growing number of applications including magnet-mediated drug delivery and image-guided therapy. Currently, lipid-based formulations are prepared by multistep protocols. Simplification of the current multistep procedures can lead to a number of important technological advantages including significantly decreased processing time, higher reaction yield, better product reproducibility, and improved quality. Here, we introduce a one-pot, single-step synthesis of drug-loaded magnetic multimicelle aggregates (MaMAs), which is based on controlled flow infusion of an iron oxide nanoparticle/lipid mixture into an aqueous drug solution under ultrasonication. Furthermore, we prepared molecular-targeted MaMAs by directional antibody conjugation through an Fc moiety using Cu-free click chemistry. Fluorescence imaging and quantification confirmed that antibody-conjugated MaMAs showed high cell-specific targeting that was enhanced by magnetic delivery.
基于脂质的制剂提供了一种纳米技术平台,由于具有生物相容性、降低毒性、相对容易进行表面修饰以及能够有效负载药物、生物制剂和纳米颗粒等优点,因此被广泛应用于各种生物医学应用中。将基于脂质的制剂与氧化铁等磁性纳米颗粒结合使用,在越来越多的应用中显示出高度的优势,包括磁介导药物输送和图像引导治疗。目前,基于脂质的制剂是通过多步方案制备的。简化当前的多步程序可以带来许多重要的技术优势,包括显著缩短处理时间、提高反应产率、更好的产品重现性和提高质量。在这里,我们介绍了一种基于超声的氧化铁纳米颗粒/脂质混合物受控流注入载药磁性多胶束聚集体(MaMAs)的一锅一步合成方法。此外,我们还通过无铜点击化学通过 Fc 部分将靶向分子的 MaMAs 定向偶联。荧光成像和定量证实,抗体偶联的 MaMAs 显示出高细胞特异性靶向性,通过磁传递得到增强。