Molecularly imprinted polymers (MIPs)
and aptamers, as effective
mimics of antibodies, can overcome only some drawbacks of antibodies.
Since they have their own advantages and disadvantages, the combination
of MIPs with aptamers could be an ideal solution to produce hybrid
alternatives with improved properties and desirable features. Although
quite a few attempts have been made in this direction, a facile and
controllable approach for the preparation of aptamer–MIP hybrids
still remains lacking. Herein, we present a new approach for facile
and controllable preparation of aptamer–MIP hybrids for high-specificity
and high-affinity recognition toward proteins. An aptamer that can
bind the glycoprotein alkaline phosphatase (ALP) with relative weak
affinity and specificity was used as a ligand, and controllable oriented
surface imprinting was carried out with an in-water self-polymerization
system of dopamine. A thin layer of polydopamine was formed to cover
the template to an appropriate thickness. After removing the template
from the polymer, an aptamer–MIP hybrid with apparently improved
affinity and specificity toward ALP was obtained, giving cross-reactivity
of 3.2–5.6% and a dissociation constant of 1.5 nM. With this
aptamer–MIP hybrid, a plasmonic immunosandwich assay (PISA)
was developed. Reliable detection of ALP in human serum by the PISA
was demonstrated.
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.
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