Applications of Cell Surface Engineering in Monocytes/Macrophages

Engineering cell surfaces with natural or synthetic materials is a unique and powerful strategy to modulate cell function, including monocytes and macrophages. This sophisticated technology utilizes engineering, chemistry, and biology techniques to conjugate cell surface with natural ligands, functional biological components, or synthetic materials to provide new characteristics and functions to cells.

Importance of Cell Surface Engineering in Monocytes/Macrophages

Monocytes are an important type of white blood cells that form macrophages and dendritic cells, representing 10% of the leukocytes in humans and playing key roles in inflammation, infection, and homeostasis. Monocytes and macrophages share many common biological functions and the conversion from monocytes to macrophages is a highly dynamic process in vivo. Monocytes/macrophages have shown multifaceted advantages in drug delivery, including but not limited to:

• Monocytes/macrophages can be actively recruited to the inflammatory tissues;
• Monocytes/macrophages have the ability to cross complicated biological barriers, migrate, and penetrate some hypoxic or poorly vascularized parts inside tumors;
• Monocytes/macrophages have a long lifespan which prolongs the circulation of encapsulated therapeutics or nanoparticles through the avoidance of immune recognition.

Over the past decade, modification of monocytes/macrophages surfaces with natural or synthetic materials (cell receptors and respective ligands, downstream signaling pathways, external stimuli, and nanomaterials) has been exploited to enhance their efficiency of drug delivery and immune modulation.

Fig.1 Representation of the cell surface structures and the principal methodologies used for cell engineering. (Custódio, 2016)

Applications of Cell Surface Engineering in Monocytes/Macrophages

• Case 1

Sugimoto et al. performed surface modification of live macrophages with tumor-targeting nucleic acid aptamers through metabolically mediated indirect conjugation method. Firstly, they added N-methacryloyl mannosamine to macrophages and then metabolically converted them into the methacryloyl group that was included in the sialic acid on the cell surface. Secondly, they conjugated the methacryloyl group-modified macrophages with thiol-terminated aptamers through a thiol-ene click reaction. These surface-modified macrophages showed an enhanced capture of apoptotic tumor cells and presentation of major histocompatibility complexes from tumor cells. Moreover, this surface modification did not induce any undesirable activation of macrophages.

• Case 2

To use macrophages' inherent hypoxia-targeting ability and minimize the toxic effect of encapsulated anticancer drugs on the viability, Holden et al. designed a macrophage-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery by hybridizing macrophages with nanoparticles through cell surface modification. They immobilized nanoparticles on the cell surface which provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles.

• Case 3

Cao et al. used the native homing property of macrophages to the tumor microenvironments and then engineered the macrophage membrane by loading the anticancer drug emtansine to target the lung metastatic sites of breast cancer. They fused the macrophage membrane with liposomal emtansine via the liposome fusion method. The results were inspiring: 1) increased cellular uptake of the emtansine liposome in metastatic 4T1 breast cancer cells; 2) inhibitory effects on cell viability; 3) enabled the liposome to target metastatic cells and produced a notable inhibitory effect on lung metastasis of breast.

Surface-engineering is already being applied to many biomedical areas, such as bioimaging, cell therapy, tissue engineering, cell tracking and sensing, drug delivery, and immune modulation. With the rapid development of new biological tools, many endeavors have been made to develop surface engineering techniques to endow cells with new functions. Based on leading-edge facilities and profound knowledge, Creative Biolabs is dedicated to offering high-quality monocytes/macrophages engineering services to enhance drug delivery efficiency and modulate immunity, such as the antigen-capturing ability, recognition, and presentation of macrophages.

References

1. Custódio, C. A.; Mano, J. F. Cell surface engineering to control cellular interactions. ChemNanoMat. 2016, 2(5): 376-384.
2. Sugimoto, S.; Iwasaki, Y. Surface modification of macrophages with nucleic acid aptamers for enhancing the immune response against tumor cells. Bioconjugate chemistry. 2018, 29(12): 4160-4167.
3. Holden, C. A.; et al. Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery. International journal of nanomedicine. 2010, 5: 25.
4. Cao, H.; et al. Liposomes coated with isolated macrophage membrane can target lung metastasis of breast cancer. ACS nano. 2016, 10(8): 7738-7748.