Shi Xiangyang, Majoros István J, Patri Anil K, Bi Xiangdong, Islam Mohammad T, Desai Ankur, Ganser T Rose, Baker James R
Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, MI 48109, USA.
Analyst. 2006 Mar;131(3):374-81. doi: 10.1039/b515624f. Epub 2006 Jan 18.
Poly(amidoamine) (PAMAM) dendrimer-based nanodevices are of recent interest in targeted cancer therapy. Characterization of mono- and multifunctional PAMAM-based nanodevices remains a great challenge because of their molecular complexity. In this work, various mono- and multifunctional nanodevices based on PAMAM G5 (generation 5) dendrimer were characterized by UV-Vis spectrometry, (1)H NMR, size exclusion chromatography (SEC), and capillary electrophoresis (CE). CE was extensively utilized to measure the molecular heterogeneity of these PAMAM-based nanodevices. G5-FA (FA denotes folic acid) conjugates (synthesized from amine-terminated G5.NH(2) dendrimer, approach 1) with acetamide and amine termini exhibit bimodal or multi-modal distributions. In contrast, G5-FA and bifunctional G5-FA-MTX (MTX denotes methotrexate) conjugates with hydroxyl termini display a single modal distribution. Multifunctional G5.Ac(n)-FI-FA, G5.Ac(n)-FA-OH-MTX, and G5.Ac(n)-FI-FA-OH-MTX (Ac denotes acetamide; FI denotes fluorescein) nanodevices (synthesized from partially acetylated G5 dendrimer, approach 2) exhibit a monodisperse distribution. It indicates that the molecular distribution of PAMAM conjugates largely depends on the homogeneity of starting materials, the synthetic approaches, and the final functionalization steps. Hydroxylation functionalization of dendrimers masks the dispersity of the final PAMAM nanodevices in both synthetic approaches. The applied CE analysis of mono- and multifunctional PAMAM-based nanodevices provides a powerful tool to evaluate the molecular heterogeneity of complex dendrimer conjugate nanodevices for targeted cancer therapeutics.
基于聚酰胺 - 胺（PAMAM）树枝状大分子的纳米器件在靶向癌症治疗方面最近受到关注。由于其分子复杂性，对基于单功能和多功能PAMAM的纳米器件进行表征仍然是一个巨大的挑战。在这项工作中，通过紫外 - 可见光谱法、核磁共振氢谱（¹H NMR）、尺寸排阻色谱法（SEC）和毛细管电泳法（CE）对基于PAMAM G5（第5代）树枝状大分子的各种单功能和多功能纳米器件进行了表征。CE被广泛用于测量这些基于PAMAM的纳米器件的分子异质性。具有乙酰胺和胺端基的G5 - FA（FA表示叶酸）缀合物（由胺端基的G5.NH₂树枝状大分子合成，方法1）呈现双峰或多峰分布。相比之下，具有羟基端基的G5 - FA和双功能G5 - FA - MTX（MTX表示甲氨蝶呤）缀合物呈现单峰分布。多功能G5.Ac(n) - FI - FA、G5.Ac(n) - FA - OH - MTX和G5.Ac(n) - FI - FA - OH - MTX（Ac表示乙酰胺；FI表示荧光素）纳米器件（由部分乙酰化的G5树枝状大分子合成，方法2）呈现单分散分布。这表明PAMAM缀合物的分子分布在很大程度上取决于起始材料的均匀性、合成方法和最终功能化步骤。在两种合成方法中，树枝状大分子的羟基化功能化掩盖了最终PAMAM纳米器件的分散性。所应用的对基于单功能和多功能PAMAM的纳米器件的CE分析为评估用于靶向癌症治疗的复杂树枝状大分子缀合物纳米器件的分子异质性提供了一个强大的工具。
