Protein corona composition modulates uptake of polymeric micelles by colorectal cancer cells

Protein corona formation on nanoparticles affects their biological interactions and fate. Polymeric micelles (PMs), preferred nanocarriers for poorly water-soluble drugs, have unclear behaviors in biological environments. This study examines the protein corona compositions of PMs formed from poly(ethylene oxide)-<i>block</i>-poly(ε-caprolactone) (PEO-PCL) and PEO-<i>block</i>-poly(α-benzyl carboxylate-ε-caprolactone) (PEO-PBCL) copolymers with varying degrees of polymerization after incubation in human plasma, and explores their relationship with cellular uptake by colorectal cancer cells. Traceable block copolymers were synthesized, self-assembled into PMs (44-99 nm, slightly negative zeta potentials), and characterized. Protein coronas were formed by incubating PMs with human plasma; protein-coated micelles were separated and analyzed. Uptake of selected PMs, with and without human plasma pre-incubation, by colorectal cancer cells was assessed. PEO-PCL micelles exhibited higher cellular uptake than PEO-PBCL micelles. Human plasma significantly reduced the uptake of PEO-PCL micelles, while PEO-PBCL micelles' uptake remained low. Proteomic analysis identified 23 distinct proteins among the combined top 20 most abundant proteins from each PM corona, with 18 common across all micelle types. In the top 10 proteins, PEO-PCL micelles shared an identical profile, whereas PEO-PBCL micelles had two unique proteins not present in PEO-PCL coronas. Protein corona composition in both PMs was shown to influence their cellular uptake behavior.