posted on 2023-12-01, 19:00authored byMengwen Song, Ruiyuan Cao, Xingjuan Chen, Cui Wang, Xiaowen Xing, Wei Li, Yuexiang Li, Yajin Liao, Wu Zhong, Qihong Li, Zhiqiang Liu
Targeting
nanoparticles (NPs) based on the specific binding of
ligands with molecular targets provides a promising tool for tissue-selective
drug delivery. However, the number of molecular targets on the cell
surface is limited, hindering the number of NPs that can bind and,
thus, limiting the therapeutic outcome. Although several strategies
have been developed to enhance drug delivery, such as enhancing drug
loading and circulation time or increasing the enhanced permeability
and retention effect of nanocarriers, none have resolved this issue.
Herein, we designed a simple method for amplified and targeted drug
delivery using two matched NPs. One NP was aptamer-functionalized
to specifically bind to target cells, while the other was aptamer-complementary
DNA-functionalized to specifically bind to aptamer-NPs. Alternate
administration of the two matched NPs enables their continuous accumulation
in the disease site despite their limited molecular targets. As a
proof of concept, the method was tested in a breast cancer model and
significantly enhanced chemotherapy of tumor cells in vitro and in vivo. The potential applications of this
method in a brain injury model were also demonstrated. Overall, the
study describes a method for amplified targeted drug delivery independent
of the target number.