Evaluating the impact of chaotropic salts on protein corona formation on polyethylene glycol-b-polylactic acid...

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⁺) < CaCl₂ (Ca²⁺) < MgCl₂ (Mg²⁺)] 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.