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An Intelligent DNA Nanorobot with in Vitro Enhanced Protein Lysosomal Degradation of HER2
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posted on 2019-06-05, 00:00 authored by Wenjuan Ma, Yuxi Zhan, Yuxin Zhang, Xiaoru Shao, Xueping Xie, Chenchen Mao, Weitong Cui, Qian Li, Jiye Shi, Jiang Li, Chunhai Fan, Yunfeng LinDNA nanorobots have emerged as new
tools for nanomedicine with
the potential to ameliorate the delivery and anticancer efficacy of
various drugs. DNA nanostructures have been considered one of the
most promising nanocarriers. In the present study, we report a DNA
framework-based intelligent DNA nanorobot for selective lysosomal
degradation of tumor-specific proteins on cancer cells. We site-specifically
anchored an anti-HER2 aptamer (HApt) on a tetrahedral framework nucleic
acid (tFNA). This DNA nanorobot (HApt-tFNA) could target HER2-positive
breast cancer cells and specifically induce the lysosomal degradation
of the membrane protein HER2. An injection of the DNA nanorobot into
a mouse model revealed that the presence of tFNA enhanced the stability
and prolonged the blood circulation time of HApt, and HApt-tFNA could
therefore drive HER2 into lysosomal degradation with a higher efficiency.
The formation of the HER2-HApt-tFNA complexes resulted in the HER2-mediated
endocytosis and digestion in lysosomes, which effectively reduced
the amount of HER2 on the cell surfaces. An increased HER2 digestion
through HApt-tFNA further induced cell apoptosis and arrested cell
growth. Hence, this novel DNA nanorobot sheds new light on targeted
protein degradation for precision breast cancer therapy.
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precision breast cancer therapyanti-HER 2 aptamerHER 2 digestionmembrane protein HER 2.Intelligent DNA NanorobotHApt-tFNAHER 2-positive breast cancer cellsHER 2 DNA nanorobotsVitro Enhanced Protein Lysosomal DegradationHER 2-mediated endocytosislysosomal degradationnovel DNA nanorobotHER 2-HApt complexesblood circulation timeHER 2DNA nanorobot
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