Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.