Although
protein therapeutics is of significance in therapeutic intervention of
cancers, controlled delivery of therapeutic
proteins still faces substantial challenges including susceptibility to degradation and denaturation and poor membrane permeability. Herein, we report a
sialic acid (SA)-imprinted biodegradable
silica nanoparticles (BS-NPs)-based
protein delivery strategy for targeted
cancer therapy. Cytotoxic
ribonuclease A (
RNase A) was effectively caged in the matrix of
disulfide-hybridized
silica NPs (encapsulation efficiency of ∼64%), which were further functionalized with
cancer targeting capability via surface imprinting with SA as imprinting template. Such nanovectors could not only maintain high stability in physiological conditions but also permit redox-triggered biodegradation for both concomitant release of the loaded therapeutic cargo and in vivo clearance. In vitro experiments confirmed that the SA-imprinted
RNase A@BS-NPs could selectively target SA-overexpressed
tumor cells, promote cells uptake, and subsequently be cleaved by intracellular
glutathione (GSH), resulting in rapid release kinetics and enhanced cell cytotoxicity. In vivo experiments further confirmed that the SA-imprinted
RNase A@BS-NPs had specific
tumor-targeting ability and high therapeutic efficacy of
RNase A in xenograft
tumor model. Due to the specific targeting and traceless GSH-stimulated intracellular
protein release, the SA-imprinted BS-NPs provided a promising platform for the delivery of biomacromolecules in
cancer therapy.