Stem
cells have been widely studied in cell biology and utilized
in cell-based therapies, and fishing stem cells from marrow is highly
challenging due to the ultralow content. Herein, a physically cross-linked
DNA network-based cell fishing strategy is reported, achieving efficient
capture, 3D envelop, and enzyme-triggered release of bone marrow mesenchymal
stem cells (BMSCs). DNA network is constructed via a double rolling
circle amplification method and through the intertwining and self-assembly
of two strands of ultralong DNA chains. DNA-chain-1 containing aptamer
sequences ensures specific anchor with BMSCs from marrow. Hybridization
between DNA-chain-1 and DNA-chain-2 enables the cross-link of cell-anchored
DNA chains to form a 3D network, thus realizing cell envelop and separation.
DNA network creates a favorable microenvironment for 3D cell culture,
and remarkably the physically cross-linked DNA network shows no damage
to cells. DNA network is digested by nuclease, realizing the deconstruction
from DNA network to fragments, and achieving enzyme-triggered cell
release; after release, the activity of cells is well maintained.
The strategy provides a powerful and effective method for fishing
stem cells from tens of thousands of nontarget cells.
Soft organisms such as earthworms can access confined, narrow spaces, inspiring scientists to fabricate soft robots for in vivo manipulation of cells or tissues and minimally invasive surgery. We report a super‐soft and super‐elastic magnetic DNA hydrogel‐based soft robot (DNA robot), which presents a shape‐adaptive property and enables magnetically driven navigational locomotion in confined and unstructured space. The DNA hydrogel is designed with a combinational dynamic and permanent crosslinking network through chain entanglement and DNA hybridization, resulting in shear‐thinning and cyclic strain properties. DNA robot completes a series of complex magnetically driven navigational locomotion such as passing through narrow channels and pipes, entering grooves and itinerating in a maze by adapting and recovering its shape. DNA robot successfully works as a vehicle to deliver cells in confined space by virtue of the 3D porous networked structure and great biocompatibility.
The efficient isolation of immune cells with high purity and low
cell damage is important for immunotherapy and remains highly challenging.
We herein report a cell capture DNA network containing polyvalent
multimodules for the specific isolation and in situ incubation of T lymphocytes (T-cells). Two ultralong DNA chains
synthesized by an enzymatic amplification process were rationally
designed to include functional multimodules as cell anchors and immune
adjuvants. Mutually complementary sequences facilitated the formation
of a DNA network and encapsulation of T-cells, as well as offering
cutting sites of a restriction enzyme for the responsive release of
T-cells and immune adjuvants. The purity of captured tumor-infiltrating
T-cells reached 98%, and the viability of T-cells maintained ∼90%.
The T-cells-containing DNA network was further administrated to a
tumor lesion for localized immunotherapy. Our work provides a robust
nanobiotechnology for efficient isolation of immune cells and other
biological particles.
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