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2015 ; 6
(9
): 972-6
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Novel DNA Polymer for Amplification Pretargeting
#MMPMID26396682
Li X
; Huang Q
; Xiao J
; Liu G
; Dou S
; Rusckowski M
; Shi H
; Liu Y
; Cheng D
ACS Med Chem Lett
2015[Sep]; 6
(9
): 972-6
PMID26396682
show ga
In this Letter, different from conventional pretargeting, an additional novel DNA
polymer with multiple copies of a target was first designed to be administrated
between the antitumor antibody, and the labeled effector served as an
amplification pretargeting strategy. Two phosphorothioate DNA strands, a bridging
and a target strand, were hybridized to form a polymer. Polymer size, as a
function of molar ratios, was then monitored by size exclusion HPLC and
electrophoretic mobility shift assay. Moreover, binding efficiency of polymers
with the radiolabeled effector and polymer size after hybridization were measured
by HPLC as well. As the polymer was expected to produce more binding sites that
would be targeted by effectors, amplification pretargeting can greatly improve
accumulation of effectors in tumor. This novel proof-of-concept was then well
demonstrated by the in vitro test of signal amplification in antibody-binding
protein L coated plate and LS174T cells. Compared to conventional pretargeting,
significantly increasing radioactive signal was observed in this designed
amplification pretargeting, which would serve as a useful paradigm of the
potential of oligomer polymers to improve pretargeting and other related
approaches.
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