聚（丙烯亚胺）树枝状大分子可以与 PEG 和白蛋白表面的 PEG 化白蛋白结合：PEG 化平台的生物物理检查以传输阳离子树枝状纳米粒子,Biopolymers

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聚（丙烯亚胺）树枝状大分子可以与 PEG 和白蛋白表面的 PEG 化白蛋白结合：PEG 化平台的生物物理检查以传输阳离子树枝状纳米粒子
Biopolymers ( IF 3.2 ) Pub Date : 2020-06-16 , DOI: 10.1002/bip.23386
Karol Ciepluch ₁ , Ralf Biehl ₂ , Maria Bryszewska ₃ , Michał Arabski ₁

Affiliation

阳离子树枝状大分子被认为是体内最好的药物转运蛋白之一。然而，为了提高它们的生物相容性，需要对其进行修饰以降低毒性。这样，许多树枝状大分子可能会失去其原始特性，例如抗癌。为了提高树枝状聚合物的生物相容性，可以将它们与白蛋白复合，这在药物递送中经常发生。然而，树枝状聚合物与白蛋白的相互作用会导致蛋白质结构破坏或根本没有复合。因此，通过荧光、圆二色性、小角 X 射线散射 (SAXS) 和透射电子显微镜对阳离子聚（丙烯亚胺）树枝状大分子和聚乙二醇（PEG）白蛋白之间的相互作用进行了研究。结果表明，阳离子树枝状聚合物在 PEG 和白蛋白表面与聚乙二醇化白蛋白结合。获得的 5k-PEG 结果表明树枝状聚合物优先结合到 PEG。对于 20k-PEG，树枝状聚合物与 PEG 和蛋白质的结合可以诱导 PEG 链塌陷到蛋白质表面。这为使用聚乙二醇化白蛋白作为携带树枝状大分子而不改变白蛋白结构的平台开辟了新的可能性，并在不进一步修饰的情况下改善了树枝状大分子的药代动力学特性。

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Poly(propylene imine) dendrimers can bind to PEGylated albumin at PEG and albumin surface: Biophysical examination of a PEGylated platform to transport cationic dendritic nanoparticles

Cationic dendrimers are considered one of the best drug transporters in the body. However, in order to improve their biocompatibility, modification of them is required to reduce toxicity. In this way, many dendrimers may lose their original properties, for example, anticancer. To improve biocompatibility of dendrimers, it is possible to complex them with albumin, as is done very often in drug delivery. However, the interaction of dendrimers with albumin can lead to protein structure disruption or no complexation at all. Therefore, the investigation of the interaction between cationic poly‐(propylene imine) dendrimers and polyethylene glycol (PEG)‐albumin by fluorescence, circular dichroism, small angle X‐ray scattering (SAXS), and transmission electron microscopy was carried out. Results show that cationic dendrimers bind to PEGylated albumin at PEG and albumin surfaces. The obtained results for 5k‐PEG indicate a preferential binding of the dendrimers to PEG. For 20k‐PEG binding of dendrimers to PEG and protein could induce a collapse of the PEG chain onto the protein surface. This opens up new possibilities to the use of PEGylated albumin as a platform to carry dendrimers without changing the albumin structure and improve the pharmacokinetic properties of dendrimers without further modification.

更新日期：2020-06-16

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