One
of the most daunting challenges of nanomedicine is the finding
of appropriate targeting agents to deliver suitable payloads precisely
to cells affected by malignancies. Even more complex is the ability
to ensure that the nanosystems enter those cells. Here, we use 2 nm
(metal core) gold nanoparticles to target human hepatocellular carcinoma
(HepG2) cells stably transfected with the SERPINB3 (SB3) protein.
The nanoparticles were coated with a 85:15 mixture of thiols featuring,
respectively, a phosphoryl choline (to ensure water solubility and
biocompatibility) and a 28-mer peptide corresponding to the amino
acid sequence 21–47 of the hepatitis B virus-PreS1 protein
(PreS1(21–47)). Conjugation of the peptide was performed via
the maleimide–thiol reaction in methanol, allowing the use
of a limited amount of the targeting molecule. This is an efficient
procedure also in the perspective of selecting libraries of new targeting
agents. The rationale behind the selection of the peptide is that
SB3, which is undetectable in normal hepatocytes, is overexpressed
in hepatocellular carcinoma and in hepatoblastoma and has been proposed
as a target of the hepatitis B virus (HBV). For the latter, the key
recognition element is the PreS1(21–47) peptide, which is a
fragment of one of the proteins composing the viral envelope. The
ability of the conjugated nanoparticles to bind the target protein
SB3, expressed in liver cancer cells, was investigated by surface
plasmon resonance analysis and in vitro via cellular uptake analysis
followed by atomic absorption analysis of digested samples. The results
showed that the PreS1(21–47) peptide is a suitable targeting
agent for cells overexpressing the SB3 protein. Even more important
is the evidence that the gold nanoparticles are internalized by the
cells. The comparison between the surface plasmon resonance analysis
and the cellular uptake studies suggests that the presentation of
the protein on the cell surface is critical for efficient recognition.
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