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Abstract：
An approach for reducing toxicity and enhancing therapeutic potential of supramolecular polyamine phosphate nanoparticles (PANs) through PEGylation of polyamines before their assembly into nanoparticles is presented here. It is shown that the number of polyethylene glycol (PEG) chains for polyamine largely influence physico-chemical properties of PANs and their biological endpoints. Poly(allylamine hydrochloride) (PAH) are functionalized through carbodiimide chemistry with three ratios of PEG molecules per PAH chain: 0.1, 1, and 10. PEGylated PAH is then assembled into PANs by exposing the polymer to phosphate buffer solution. PANs decrease size and surface charge with increasing PEG ratios as evidenced by dynamic light scattering and zeta potential measurements, with the ten PEG/PAH ratio PANs having practically zero charge. Small angle X-ray scattering (SAXS) proves that PEG chains form a shell around a polyamine core, which is responsible for the screening of positive charges. MTT experiments show that the screening of amine groups decreases nanoparticle toxicity, with the lowest toxicity for the 10 PEG/PAH ratio. Fluorescence correlation spectroscopy (FCS) proves less interaction with proteins for PEGylated PANs. Positron emission tomography (PET) imaging of 18 F labelled PANs shows longer circulation time in healthy mice for PEGylated PANs than non-PEGylated ones.
摘要：
本文提出了一种通过聚胺在组装成纳米颗粒之前进行聚乙二醇化来降低超分子聚胺磷酸盐纳米颗粒（PAN）的毒性并增强其治疗潜力的方法。结果表明，聚胺的聚乙二醇（PEG）链的数量在很大程度上影响了PAN的物理化学性质及其生物学终点。聚(烯丙胺盐酸盐)(PAH)通过碳二亚胺化学官能化,每个PAH链具有三种PEG分子比率:0.1、1和10。然后通过将聚合物暴露于磷酸盐缓冲溶液而将PEG化的PAH组装成PAN。PAN随着PEG比率的增加而减小尺寸和表面电荷，如动态光散射和ζ电位测量所证明的。十个PEG/PAH比率PAN几乎为零电荷。小角度X射线散射（SAXS）证明PEG链在多胺核周围形成壳，负责正电荷的筛选。MTT实验表明，胺基的筛选降低了纳米颗粒的毒性，对于10个PEG/PAH比率，毒性最低。荧光相关光谱(FCS)证明与聚乙二醇化PAN的蛋白质的相互作用较小。18F标记的PAN的正电子发射断层扫描（PET）成像显示，健康小鼠的聚乙二醇化PAN循环时间比非聚乙二醇化PAN更长。
