Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Department of Biomedical Engineering, Purdue School of Engineering & Technology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Carbohydr Polym. 2020 Apr 15;234:115901. doi: 10.1016/j.carbpol.2020.115901. Epub 2020 Jan 25.
A therapeutic nanocarrier capable of cell targeting has the potential to reduce off-target effects of otherwise effective drugs. Nanoparticle surface modification can be tailored for specific cells, however multistep surface modification can prove slow and difficult for a variety of cell types. Here, we designed drug carrying polysaccharide based nanoparticles with a layered structure for clickable surface modification. The center of nanoparticle was composed of cationic macromer (e.g., poly-l-lysine) and anionic polysaccharide (e.g., heparin). Furthermore, a 'clickable' polysaccharide was installed on the surface of the nanoparticles to permit a wide range of bioconjugation via norbornene-tetrazine click chemistry. The utilities of these layered nanoparticles were demonstrated via enhanced protein sequestration, selective cell targeting (via PEGylation or altering polysaccharide coating), as well as loading and release of chemotherapeutic. The drug-loaded nanocarriers proved cytotoxic to J774A.1 monocytes and MOLM-14 leukemia cells.
一种能够靶向细胞的治疗性纳米载体有可能降低 otherwise effective drugs 的脱靶效应。纳米颗粒表面修饰可以针对特定的细胞进行定制，然而，对于多种细胞类型，多步表面修饰可能会证明缓慢而困难。在这里，我们设计了具有层状结构的载药多糖基纳米颗粒，用于可点击的表面修饰。纳米颗粒的中心由阳离子大分子（例如聚赖氨酸）和阴离子多糖（例如肝素）组成。此外，在纳米颗粒的表面安装了“可点击”多糖，以允许通过降冰片烯-四嗪点击化学进行广泛的生物偶联。通过增强蛋白质隔离、选择性细胞靶向（通过 PEGylation 或改变多糖涂层）以及化疗药物的负载和释放，证明了这些层状纳米颗粒的实用性。载药纳米载体对 J774A.1 单核细胞和 MOLM-14 白血病细胞具有细胞毒性。
