An ability to promote therapeutic immune cells to recognize cancer cells is important for the success of cell‐based cancer immunotherapy. We present a synthetic method for functionalizing the surface of natural killer (NK) cells with a supramolecular aptamer‐based polyvalent antibody mimic (PAM). The PAM is synthesized on the cell surface through nucleic acid assembly and hybridization. The data show that PAM has superiority over its monovalent counterpart in powering NKs to bind to cancer cells, and that PAM‐engineered NK cells exhibit the capability of killing cancer cells more effectively. Notably, aptamers can, in principle, be discovered against any cell receptors; moreover, the aptamers can be replaced by any other ligands when developing a PAM. Thus, this work has successfully demonstrated a technology platform for promoting interactions between immune and cancer cells.

Molecular recognition is essential to the development of biomaterials. Aptamers are a unique class of synthetic ligands interacting with not only their target molecules with high affinities and specificities but also their complementary sequences with high fidelity. Thus, aptamers have recently attracted significant attention in the development of an emerging class of biomaterials, that is, aptamer‐functionalized hydrogels. In this review, we introduce the methods of incorporating aptamers into hydrogels as pendant motifs or crosslinkers. We further introduce the functions of these hydrogels in recognizing proteins, cells, and analytes through four applications including protein delivery, cell capture, regenerative medicine, and molecular biosensing. Notably, as aptamer‐functionalized hydrogels have the characteristics of both aptamers and hydrogels, their potential applications are broad and beyond the scope of this review. This article is categorized under: Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Emerging Technologies

Overexpression of proteins in the body can cause severe diseases and other physiological disturbances. The development of protein blockers and local delivery systems would offer opportunities for addressing the health problems caused by protein overexpression. Nucleic acid aptamers are an emerging class of ligands with the potential to block proteins effectively; however, little effort has been made in developing polymer systems for local aptamer delivery. In this work, polymer microneedles capable of delivering DNA aptamers locally to inhibit the function of vascular endothelial growth factor (VEGF) were developed and studied. The presence of anti-VEGF aptamer in the polymer matrix did not change the apparent mechanical strength of the microneedles. Once in contact with a physiological solution, the polymer microneedles quickly dissolved, generating a high concentration of anti-VEGF aptamer in the surrounding local microenvironment. Aptamer delivery by way of dissolving polymer microneedles in a tissue phantom reduced VEGF-mediated endothelial cell tube formation. Thus, aptamer-loaded polymer microneedles hold great potential as a therapeutic tool for the treatment of human diseases resulting from protein overexpression.

The cell surface can be engineered with synthetic DNA for various applications ranging from cancer immunotherapy to tissue engineering. However, while elegant methods such as click conjugation and lipid insertion have been developed to engineer the cell surface with DNA, little effort has been made to systematically evaluate and compare these methods. Resultantly, it is often challenging to choose a right method for a certain application or to interpret data from different studies. In this study, we systematically evaluated click conjugation and lipid insertion in terms of cell viability, engineering efficiency, and displaying stability. Cells engineered with both methods can maintain high viability when the concentration of modified DNA is less than 25–50 μM. However, lipid insertion is faster and more efficient in displaying DNA on the cell surface than click conjugation. The efficiency of displaying DNA with lipid insertion is 10–40 times higher than that with click conjugation for a large range of DNA concentration. However, the half-life of physically inserted DNA on the cell surface is 3–4 times lower than that of covalently conjugated DNA, which depends on the working temperature. While the half-life of physically inserted DNA molecules on the cell surface is shorter than that of DNA molecules clicked onto the cell surface, lipid insertion is more effective than click conjugation in the promotion of cell–cell interactions under the two different experimental settings. The data acquired in this work are expected to act as a guideline for choosing an approximate method for engineering the cell surface with synthetic DNA or even other biomolecules.

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