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首页> 外文期刊>RSC Advances >Engineering of NIR fluorescent PEGylated poly(RGD) proteinoid polymers and nanoparticles for drug delivery applications in chicken embryo and mouse models
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Engineering of NIR fluorescent PEGylated poly(RGD) proteinoid polymers and nanoparticles for drug delivery applications in chicken embryo and mouse models

机译：NIR荧光聚乙二醇化聚（RGD）蛋白质聚合物的工程和纳米粒子用于鸡胚和小鼠模型的药物递送应用

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Proteinoids are non-toxic biodegradable polymers based on thermal step-growth polymerization of natural or synthetic amino acids. Hollow proteinoid nanoparticles (NPs) may then be formed via a self-assembly process of the proteinoid polymers in an aqueous solution. In the present article polymers and NPs based on D -arginine, glycine and L -aspartic acid, poly(R ~(D) GD), were synthesized for tumor targeting, particularly due to the high affinity of the RGD motif to areas of angiogenesis. Near IR fluorescent P(R ~(D) GD) NPs were prepared by encapsulating the fluorescent NIR dye indocyanine green (ICG) within the formed P(R ~(D) GD) NPs. Here, we investigate the effect of the covalent conjugation of polyethylene glycol (PEG), with different molecular weights, to the surface of the near IR encapsulated P(R ~(D) GD) NPs on the release of the dye to human serum due to bio-degradation of the proteinoid NPs and on the uptake by tumors. This work illustrates that the release of the encapsulated ICG from the non-PEGylated NPs is significantly faster than for that observed for the PEGylated NPs, and that the higher molecular weight is the bound PEG spacer the slower is the dye release profile. In addition, in a chicken embryo model, the non-PEGylated ICG-encapsulated P(R ~(D) GD) NPs exhibited a higher uptake in the tumor region in comparison to the PEGylated ICG-encapsulated P(R ~(D) GD) NPs. However, in a tumor xenograft mouse model, which enables a prolonged experiment, the importance of the PEG is clearly noticeable, when a high concentration of PEGylated P(R ~(D) GD) NPs was accumulated in the area of the tumor compared to the non-PEGylated P(R ~(D) GD). Moreover, the length of the PEG chain plays a major role in the ability to target the tumor. Hence, we can conclude that selectivity towards the tumor area of non-PEGylated and the PEGylated ICG-encapsulated P(R ~(D) GD) NPs can be utilized for targeting to areas of angiogenesis, such as in the cases of tumors, wounds or cuts, etc.
机译：蛋白质是基于天然或合成氨基酸的热阶梯生长聚合的无毒的可生物降解聚合物。然后可以通过在水溶液中的蛋白质聚合物的自组装方法形成中空蛋白骨型纳米颗粒（NPS）。在本文的基于D -Ar钦的聚合物和NPS中，甘氨酸和L-丙酸，聚（R〜（D）Gd）被合成用于肿瘤靶向，特别是由于RGD基序对血管生成区域的高亲和力。通过将荧光NIR染料吲哚菁绿（ICG）包封在形成的P（R〜（D）GD）NPS内，制备近红外荧光P（R〜（D）GD）NPS。在这里，我们研究了聚乙二醇（PEG），用不同分子量的共价缀合对近红外封装的P（R〜（D）Gd）NPS的效果在染料到人血清的释放上蛋白含NPS和肿瘤摄取的生物降解。该工作说明，从非聚乙二醇化NPS的包封的ICG的释放比对于对聚乙二醇化的NPS观察到的释放显着快，并且较高的分子量是结合的PEG间隔物，较慢的是染料释放曲线。另外，在鸡胚模型中，与聚乙二醇化的ICG包封的P（R〜（D）GD相比，非聚乙二醇化的ICG封装的P（R〜（D）Gd）NPS在肿瘤区域中表现出更高摄取的）NPS。然而，在肿瘤异种移植小鼠模型中，当能够在肿瘤面积中积累了高浓度的聚乙二醇化的P（R〜（D）GD）NPS时，PEG的重要性显然明显明显。非聚乙二醇化的p（R〜（D）GD）。此外，PEG链的长度在靶向肿瘤的能力中起主要作用。因此，我们可以得出结论，朝向非聚乙二醇化的肿瘤面积和聚乙二醇化的ICG包封的P（R〜（D）Gd）NPS的选择性可用于靶向血管生成区域，例如在肿瘤的情况下，伤口或削减等。

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