Nanomaterials
have a great potential for use in various biorelated
applications such as drug delivery systems and in vivo imaging; understanding nanoparticle–cell interactions is
an important requisite for these applications. Herein, the nanoparticle–cell
interactions, including the cellular uptake mechanism, were investigated
in detail using polymer nanogels possessing molecular recognition
ability (molecularly imprinted polymer nanogels: MIP-NGs) capable
of protein corona regulation via albumin recognition and using refractory
cancer cell lines and an immune-related cell line. Albumin recognition
in the MIP-NGs further increased the albumin-dependent inhibition
of cellular uptake of the nanogels, including uptake by cancer cells
and macrophages. Cellular uptake was inhibited more efficiently in
MIP-NGs than in the reference nonimprinted polymer nanogels without
albumin recognition cavities. In the presence of serum albumin, MIP-NGs
did not cause a significant upregulation of inflammatory reactions
as measured by cytokine secretion by macrophages. To the best of our
knowledge, our study is the first to use molecular recognition of
albumin in nanogels to regulate the protein corona and in turn control
cellular interactions. Our results provide strong evidence that MIP-NGs
could utilize human serum albumin in the formation of a protein corona
to avoid immune responses. We hope our results can provide important
insights that translate into biomedical applications of nanomaterials.