Harnessing Biology to Deliver Therapeutic and Imaging Entities via Cell-Based Methods

Abstract

The accumulation of therapeutic and imaging agents at sites of interest is critical to their efficacy. Similarly, off-target effects (especially toxicity) are a major liability for these entities. For this reason, the use of delivery vehicles to improve the distribution characteristics of bio-active agents has become ubiquitous in the field. However, the majority of traditionally employed, cargo-bearing platforms rely on passive accumulation. Even in cases where "targeting" functionalities are used, the agents must first reach the site in order for the ligand-receptor interaction to occur. The next stage of vehicle development is the use of "recruited" entities, which respond to biological signals produced in the tissues to be targeted, resulting in improved specificities. Recently, many advances have been made in the utilization of cells as delivery agents. They are biocompatible, exhibit excellent circulation lifetimes and tissue penetration capabilities, and respond to chemotactic signals. In this Minireview, we will explore various cell types, modifications, and applications where cell-based delivery agents are used.

Keywords: biological activity; bioorganic chemistry; cancer; drug delivery; nanotechnology.

Figure 1.

Cell types employed as delivery vehicles and locations where they are recruited/used to deliver agents to.

Figure 2.

Non-covalent cellular modifications for cargo delivery. (Above) Red blood cells (red), leukocytes (pink) and stem cells (purple) have been noncovalently modified at the cell surface to display various agent types shown. (Below) Stem cells and leukocytes have the innate ability to internalize cargo shown. Specialized methods must be used for RBCs (not shown) to uptake therapeutic entities.

Figure 3.

Strategies for covalent cell surface modifications. Click chemistry methods involve coupling of metabolically incorporated azides to phosphines or alkynes for cargo delivery. NHS esters and maleimides can be used for conjugations to amines and thiols, respectively. Biotin can be linked to the cell membrane via several means, and then associate with streptavidin-related proteins linked to chemical moieties.