Cells are a basic unit of living organisms and using them as drug carriers or therapeutics has unique advantages. For instance, it can significantly improve the targeting efficiency due to the homing effects (e.g. immune cells and stem cells) or improve the systemic circulation (e.g. red blood cells). There are currently several strategies to engineer cells to afford therapeutic capability. The most common one is genetic engineering, which however involves tedious and complicated process, leading to expensive cell-based therapeutics. Non-genetic cell engineering may rely on either endocytosis of medicines intracellularly, or covalent conjugation of medicines onto the surface of cells. Additionally, biological ligand-receptor interactions can be leveraged to conjugate nanomedicine to the surface of live cells. Nevertheless, the cells that phagocytize medicines may degrade the drug before reaching the target. Covalent binding involves a complex synthetic process on the cell surface, which may impair the physiological function of the carrier cells. The ligand-receptor interaction is often limited to specific cells, and competitive ligand displacement occurs in vivo as well.

During the past several years, we have developed unique supramolecular cell engineering approaches via synthetic host-guest interactions that are mostly bioorthogonal, to tackle these above-mentioned issues and to enable targeted delivery of various nanomedicines to specific tissues, driven by the inflammatory tropism of immune cells or wound-targeting properties of platelets.¹ When required, other cells such as red blood cells may also be engineered and employed to deliver nanomedicine for extended circulation and targeted accumulation in tissues with specific microenvironment.² Two general, supramolecular cell engineering strategies were designed and development to achieve the above-discussed purpose: 1) extracellular supramolecular engineering;³ and 2) intracellular supramolecular engineering.⁴ We show that these unique systems, when designed for individual purposes, may effectively treat several key diseases including acute pneumonia,⁵ atherosclerosis,⁶ solid tumors,⁷ and ischemic stroke,⁸ respectively.