Poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) nanoparticles are widely utilized in pharmaceutical applications due to their biodegradability, controllable degradation profiles, and favorable safety records. Upon contact with biological fluids such as human serum (HS) or human plasma (HP), these nanoparticles rapidly adsorb proteins from the surrounding medium, forming a protein corona that significantly influences their in vivo fate. This corona dictates processes including immune recognition, blood circulation time, biodistribution, cellular internalization, clearance, and targeting efficiency. Understanding the factors that govern corona formation is essential for rational design of effective nanotherapeutics.
In this study, five clinically relevant Resomer® polymers were systematically investigated to evaluate the impact of four key physicochemical parameters: molecular weight, matrix hydrophobicity (defined by lactic acid/glycolic acid ratio), surface end group identity, and incubation medium (HS vs HP). All nanoparticle systems were prepared using identical methods—solvent displacement with polyvinyl alcohol (PVA) as steric stabilizer—to ensure comparability. The resulting nanoparticles exhibited similar hydrodynamic diameters (~180–225 nm), low polydispersity indices (<0.08), and consistent zeta potential values, indicating uniform colloidal stability across all batches. Protein corona analysis was performed using Bradford assay for total protein quantification, SDS-PAGE for separation, and LC-MS/MS for detailed proteomic identification. Results revealed that surface end group chemistry had the most profound influence on both the quantity and composition of bound proteins. Acid-terminated nanoparticles (502 H-NP) showed an eightfold higher protein binding capacity in HP and tenfold in HS compared to their ester-terminated counterparts (502-NP). This was attributed to stronger ionic interactions between negatively charged carboxylic acid groups on the NP surface and positively charged amino acid residues in proteins, outweighing hydrophobic interactions with the polymer backbone. Matrix hydrophobicity, defined by LA/GA ratio, showed minimal effect on total protein amount. Coronal protein levels remained comparable among 502-, 752 S-, and 202 S-NP systems despite increasing hydrophobicity. However, qualitative differences emerged: more hydrophobic particles (202 S-NP) preferentially enriched proteins associated with blood coagulation (BC) and immune response (IR), while hydrophilic surfaces (502 H-NP) favored oxygen transport-related proteins like haptoglobin and serotransferrin. Molecular weight also played a role, primarily affecting quantity rather than quality. Higher molecular weight polymers (R 207 S-NP) yielded fewer surface end groups, leading to reduced protein adsorption—consistent with decreased availability of interaction sites. Nonetheless, the types of proteins bound remained largely unchanged across different molecular weights.MAGEA4 Antibody References
Incubation medium had a negligible effect on overall corona composition.Nibrin Antibody medchemexpress While HP-specific proteins such as fibrinogen were detected only in HP-incubated samples, functional categories of the corona—including IR, LP, and OT proteins—were highly similar between HS and HP coronas.PMID:35167762 This suggests that despite differences in protein concentration and specific components, the biological behavior of the corona is driven more by NP surface properties than by the source fluid.
LC-MS/MS analysis identified 163 unique proteins across all coronas, with 502 H-NP exhibiting the highest diversity (90 proteins in HP, 77 in HS). Notably, several disease-associated proteins were selectively enriched: serum amyloid A-1 (linked to lung cancer), inter-alpha-trypsin inhibitor heavy chain H4 (cancer biomarker), and histidine-rich glycoprotein (involved in cell-matrix interactions). These findings highlight the diagnostic potential of tailored NP systems.
Functional classification revealed that immune response-initiating proteins dominated all coronas (>50%), followed by lipoproteins. The presence of apolipoproteins (ApoA-I, ApoE) suggests potential for hepatocyte targeting and brain delivery. Despite opsonization, prolonged circulation may still occur if dysopsonins prevail.
In conclusion, surface end group identity is the primary determinant of protein corona formation, followed by hydrophobicity and molecular weight. Incubation medium plays a minor role. These insights enable precise engineering of PLGA and PLA nanoparticles for enhanced therapeutic performance, where selective protein enrichment can be leveraged not only for improved targeting but also for diagnostic applications.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com