posted on 2024-01-22, 06:06authored byXiaoxue Hu, Hongli Chi, Xiaoyi Fu, Jinling Chen, Linying Dong, Shiqi Jiang, Yan Li, Jingyi Chen, Ming Cheng, Qianhao Min, Ye Tian, Penghui Zhang
Precise
mapping and regulation of cell surface receptors hold immense
significance in disease treatment, such as cancer, infection, and
neurodisorders, but also face enormous challenges. In this study,
we designed a series of adjustable multivalent aptamer-based DNA nanostructures
to precisely control their interaction with receptors in tumor cells.
By profiling surface receptors on 12 cell lines using 10 different
aptamers, we generated a heatmap that accurately distinguished between
various tumor types based on multiple markers. We then incorporated
these aptamers onto DNA origami structures to regulate receptor recognition,
with patch-like structures demonstrating a tendency to be trapped
on the cell surface and with tube-like structures showing a preference
for internalization. Through precise control of aptamer species, valence,
and geometric patterns, we found that multiheteroreceptor-mediated
recognition not only favored the specific binding of nanostructures
to tumor cells but also greatly enhanced intracellular uptake by promoting
clathrin-dependent endocytosis. Specifically, we achieved over 5-fold
uptake in different tumor cells versus normal cells using tube-like
structures modified with different diheteroaptamer pairs, facilitating
targeted drug delivery. Moreover, patch-like structures with triheteroaptamers
guided specific interactions between macrophages and tumor cells,
leading to effective immune clearance. This programmable multivalent
system allows for the precise regulation of cell recognition using
multiple parameters, demonstrating great potential for personalized
tumor treatment.