In-field
analysis (e.g., clinical and diagnostics) using nanostructured
porous silicon (PSi) for label-free optical biosensing has been hindered
so far by insufficient sensitivity of PSi biosensors. Here we report
on a label-free PSi interferometric aptasensor able to specifically
detect tumor necrosis factor alpha (TNFα, a protein biomarker
of inflammation and sepsis) at concentration down to 3.0 nM with signal-to-noise
ratio (S/N) of 10.6 and detection limit (DL) of 200 pM. This represents
a 10 000-fold improvement with respect to direct (i.e., nonamplified)
label-free PSi biosensors and pushes PSi biosensors close to the most
sensitive optical and label-free transduction techniques, e.g., surface
plasmon resonance (SPR) for which a lowest DL of 100 pM in aptasensing
has been reported. A factor 1000 in improvement is achieved by introducing
a novel signal-processing technique for the optical readout of PSi
interferometers, namely, interferogram average over wavelength (IAW)
reflectance spectroscopy. The IAW reflectance spectroscopy is shown
to significantly improve both sensitivity and reliability of PSi biosensors
with respect to commonly used fast Fourier transform (FFT) reflectance
spectroscopy. A further factor 10 is achieved by enabling preparation
of PSi interferometers with enlarged pore sizes (up to a 3× increase
in diameter) at constant current density (i.e., constant porosity
and, in turn, constant refractive index). This method is in contrast
to standard PSi preparation where pore size is increased by increasing
etching current density (i.e., porosity), and allows tackling mass-limited
diffusion of biomolecules into the nanopores without worsening PSi
interferometer optical features.
Aptamers able to bind efficiently cell-surface receptors differentially expressed in tumor and in healthy cells are emerging as powerful tools to perform targeted anticancer therapy. Here, we present a novel oligonucleotide chimera, composed by an RNA aptamer and a DNA decoy. Our assembly is able to (i) target tumor cells via an antitransferrin receptor RNA aptamer and (ii) perform selective codelivery of a chemotherapeutic drug (Doxorubicin) and of an inhibitor of a cell-survival factor, the nuclear factor κB decoy oligonucleotide. Both payloads are released under conditions found in endolysosomal compartments (low pH and reductive environment). Targeting and cytotoxicity of the oligonucleotidic chimera were assessed by confocal microscopy, cell viability, and Western blot analysis. These data indicated that the nuclear factor κB decoy does inhibit nuclear factor κB activity and ultimately leads to an increased therapeutic efficacy of Doxorubicin selectively in tumor cells.
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