表面修饰的 PAMAM 树状聚合物的细胞内化动力学和表面电荷可及性。
Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers.
机构信息
Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Autopista Concepción-Talcahuano 7100, Talcahuano, Chile.
Departamento de Fisiología, Facultad de Ciencias Biológicas, Universidad de Concepción, Barrio Universitario S/N, Concepción, Chile.
出版信息
Org Biomol Chem. 2023 Oct 4;21(38):7782-7790. doi: 10.1039/d3ob01265d.
Surface-modified PAMAM dendrimers have important applications in drug delivery, yet a gap remains about the role that surface functionalization plays on their cell internalization capacity. We examined the cell internalization kinetics of PAMAM dendrimers that were surface-modified with acetyl, folate and poly(ethylene glycol), as model functional groups differing in size, charge, and chemical functionality. Dendrimers with 25% functionalization were internalized by HEK cells, but with slower rates and lower maximum uptakes than the native dendrimer between 1-6 h of incubation. Dendrimers with 50% functionalization exhibited negligible internalization capacities at all incubation times. Molecular dynamics simulations revealed that the solvent accessibility of the cationic surface charges is a key factor affecting cell internalization, unlike the total charge, functionality or size of surface-modified PAMAM dendrimers. These findings provide valuable insights to assist the design of PAMAM-based systems for drug delivery applications.
表面修饰的 PAMAM 树枝状大分子在药物传递中有重要的应用，但对于表面功能化在其细胞内化能力中的作用仍存在差距。我们研究了表面修饰为乙酰基、叶酸和聚乙二醇的 PAMAM 树枝状大分子的细胞内化动力学，这些模型功能基团在大小、电荷和化学功能方面存在差异。25%功能化的树枝状大分子被 HEK 细胞内化，但在 1-6 小时的孵育过程中，其内化速率比天然树枝状大分子慢，最大摄取量也较低。50%功能化的树枝状大分子在所有孵育时间内都表现出可忽略不计的内化能力。分子动力学模拟表明，阳离子表面电荷的溶剂可及性是影响细胞内化的关键因素，而不是表面修饰的 PAMAM 树枝状大分子的总电荷、功能或大小。这些发现为药物传递应用中基于 PAMAM 的系统的设计提供了有价值的见解。
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