Tabah Owen, Nichols Daniel, Blake Ashley, Witt Grace, Chou Chau-Wen, Larsen Jessica
Department of Bioengineering, Clemson University, Clemson, SC, United States.
Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, SC, United States.
J Colloid Interface Sci. 2025 Dec;699(Pt 1):138195. doi: 10.1016/j.jcis.2025.138195. Epub 2025 Jun 15.
Polymersomes (PS) are a class of hollow polymeric nanoparticle vesicles made of amphiphilic block co-polymers that self-assemble via hydrophobic interactions. One of the significant unsung challenges for their translation is the uncontrolled formation of the protein corona, which can influence PS biodistribution, cellular uptake, and immune recognition. Despite the major benefits associated with PS, no studies have yet explored engineering their protein corona. Evidence suggests that the confirmation of polyethylene glycol (PEG) chains, which can vary in response to Hofmeister series salts, can affect protein corona composition. Here, we investigated the impact of different Hofmeister series salt ions, focusing on increasing chaotropic salts [NaCl (Na) < CaCl (Ca) < MgCl (Mg)] on the biomolecular identity of PEG-b-polylactic acid (PLA) PS after incubation in serum. We observed that the ionic environment significantly influences the protein corona formation on PEG-b-PLA PS. The presence of different salt ions, particularly divalent cations like calcium and magnesium, can change the size and surface chemistry of PEG-b-PLA PS, leading to alterations in the specific protein composition of the corona. We propose that these protein corona differences are driven by both (1) charge-based and (2) biologically driven interactions. This knowledge could be leveraged to engineer nanoparticles with tailored protein coronas. While this research focused primarily on PS made of one polymer, PEG-b-PLA, other polymers and polyelectrolytes in PSs need to be investigated. We've shown that a surface coated with low molecular weight PEG can be impacted by ions, despite not having any ionizable groups.
聚合物囊泡（PS）是一类由两亲性嵌段共聚物制成的中空聚合物纳米颗粒囊泡，通过疏水相互作用自组装而成。其转化面临的一个重大未被关注的挑战是蛋白质冠层的形成不受控制，这会影响PS的生物分布、细胞摄取和免疫识别。尽管PS有诸多主要优点，但尚未有研究探索对其蛋白质冠层进行工程设计。有证据表明，聚乙二醇（PEG）链的构象会因霍夫迈斯特系列盐而变化，这会影响蛋白质冠层的组成。在此，我们研究了不同霍夫迈斯特系列盐离子的影响，重点关注增加离液盐[氯化钠（Na）<氯化钙（Ca）<氯化镁（Mg）]对血清孵育后聚乙二醇-b-聚乳酸（PLA）PS生物分子特性的影响。我们观察到离子环境显著影响PEG-b-PLA PS上蛋白质冠层的形成。不同盐离子的存在，特别是钙和镁等二价阳离子，会改变PEG-b-PLA PS的大小和表面化学性质，导致冠层特定蛋白质组成发生变化。我们认为这些蛋白质冠层差异是由（1）基于电荷的相互作用和（2）生物驱动的相互作用共同驱动的。这些知识可用于设计具有定制蛋白质冠层的纳米颗粒。虽然这项研究主要集中在由一种聚合物PEG-b-PLA制成的PS上，但PS中的其他聚合物和聚电解质也需要进行研究。我们已经表明，尽管没有任何可电离基团，但涂有低分子量PEG的表面会受到离子的影响。
