Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Optimizing nanoparticle (NP) biological identity for tumor uptake is crucial for effective cancer therapy.
• Protein corona formation on NPs from biofluids can enhance tumor accumulation.
• Current NP surface modifications, like polyethylene glycol (PEG), have limitations in achieving specific biological identities.

Purpose of the Study:

• To investigate the use of sera from Influenza A virus (IAV)-infected mice to create a protein corona on hyperbranched polyester polymer NPs (HBPE-NPs).
• To evaluate if this infection-induced protein corona enhances NP uptake by cancer cells and improves drug delivery.
• To explore the potential of using immune response-derived sera to rationally design NP biological identity for targeted delivery.

Main Methods:

• HBPE-NPs encapsulating a tracking dye or cancer drug were pre-coated with sera from IAV-infected mice (VS3-6).
• Uptake of pre-coated NPs by breast cancer cells and monocytic cells (THP-1) was compared to PEG-modified NPs.
• Proteomics analysis was performed to identify proteins adsorbed onto the NP surface.
• In vivo distribution and stability of VS5-treated HBPE-NPs were assessed.

Main Results:

• Cancer cells showed significantly higher uptake of VS3-6 pre-treated HBPE-NPs compared to PEG-HBPE-NPs.
• Uptake of VS5 pre-treated HBPE-NPs by monocytic cells (THP-1) was reduced compared to PEG-HBPE-NPs.
• VS5-treated HBPE-NPs demonstrated more efficient cancer drug delivery and improved in vivo distribution.
• Proteins like thrombospondin-1 (TSP-1), capable of binding cancer cell receptors, were identified on the sera-treated NPs.
• NPs remained stable after interaction with endothelial cells.

Conclusions:

• Sera from infected hosts provide a rich source of proteins that can modulate NP biological identity.
• This approach enables the rational design of NPs for targeted uptake by specific cell types, such as cancer cells.
• Immune response-derived sera offer a promising strategy for enhancing NP-based drug delivery and tumor accumulation.