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Enhancing Cell therapies from the Outside In: Cell Surface Engineering Using Synthetic Nanomaterials

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Therapeutic treatments based on the injection of living cells are in clinical use and preclinical development for diseases ranging from cancer to cardiovascular disease to diabetes. Cell therapy involves direct transplantation, injection or fusion with living cells to treat disease, and the efficacy of cell therapy depends on proper control of its fate and function. Apart from three traditional distinct ways of cell function engineering, a fourth approach, which uses synthetic materials or chemical biology approaches to alter cell surfaces, has recently begun to gain traction. These approaches offer a powerful complement to traditional genetic engineering strategies for enhancing the function of living cells.

Synthetic nanomaterials have a significant role to play in cell surface engineering because of their unique properties and ability to provide beyond the function of single molecules to enhance the therapeutic potential of cell products in the clinic. The key applications of cell surface engineering include engineering cell adhesion and in vivo cell migration by introducing exogenous targeting ligands into the cell membranes or manipulating cell surface glycosylation.

However, studies have shown that synthetic drug nanocarriers with in vivo migration pattern can be applied to provide a wide variety of therapeutic agents, including small molecules, siRNA, contrast agents or vaccines to therapeutically desired anatomical compartments, through the use of dynamic cell-nanoparticle hybrid vehicles, which differ from conventional static drugs targeting ligands. With the combination of cell surface engineering and synthetic nanomaterials approach, cell bioengineering methodologies are ultimately poised to extend far beyond enhancing the efficacy of established cell-based therapies.

Cell-surface engineering has encountered three major challenges in its development. The first challenge is to develop criteria of clinically-viable cell surface bioengineering strategies that remain to rationally modify select cell-surface molecules without physically blocking or functionally compromising others. Secondly, the dynamic nature of the cell surface is a major challenge for cell surface engineering, which may lead to premature internalization and ultimately the degradation of surface-modified or cell-bound nanocarriers. The third key challenge to cell surface engineering is to introduce synthetic modifications that are compatible with the complex mechanical and biochemical environment the cell is exposed to in vivo.

One possible approach here is to use exogenous materials for cell surface engineering. More in detail, the materials used to modify the cell surface include recombinant proteins, imaging agents and drug-carrying nanoparticles. Researches have shown that chemical/enzymatic cell surface modifications are made using naturally recombination groups or molecules on the cell surface to achieve customized cell-surface glycosylation required by therapeutic engineers. Due to the metabolic or genetic introduction of reactive functional groups on the cell surface, the hydrophobic insertion of the cell membrane, the specific absorption of the cell, and the interaction of ligands with receptors naturally present on the cell surface, it is theoretically very suitable for the contact of nanomaterials with cells to endow donor cells with new characteristics and functions.

It is now proven that nanomaterials play a very important role in achieving stable cell surface modification that regulates the internalization of synthetic materials cell contact via the physical shape of the exogenous material. Besides, the mechanism of cell attachment plays a key role in the stability of cell surface modifications as well.

By studying cell surface engineering, scientists have gained key therapeutic results. The realization of retargeting systemic cell homing enables the donor cells to efficiently homing to the intended tissue or organ, which is crucial to the success of treatment. Moreover, the application of cell surface engineering brings lots of benefits by providing a source of autocrine growth factors for transplanted cells, using cell carriers to target drugs to the tissue sites associated with treatment, and tracking adoptively transferred cells in vivo.

Currently, there are significant investments in the development and commercialization of cell-based products for the treatment of a wide variety of diseases, including tissue degeneration, chronic inflammation, autoimmunity, genetic diseases, cancer, and infections that demonstrating a great potential of cell surface engineering.

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