Cell-Based Drug Delivery Systems with Innate Homing Capability as a Novel Nanocarrier Platform

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Nanoparticle-based drug delivery systems have been designed to treat various diseases. However, many problems remain, such as inadequate tumor targeting and poor therapeutic outcomes. To overcome these obstacles, cell-based drug delivery systems have been developed. Candidates for cell-mediated drug delivery include blood cells, immune cells, and stem cells with innate tumor tropism and low immunogenicity; they act as a disguise to deliver the therapeutic payload. Compared to conventional DDSs, cell-based systems show prolonged circulation, specific tissue tropism, superior flexibility, low immunogenicity, and cytotoxicity with unique cellular properties. Furthermore, cell-based DDSs are intrinsically biodegradable and biocompatible. The ability of therapeutically relevant cells to home toward injured tissues allows cell-based drug carriers to act as a biomimetic platform and deliver therapeutic agents to specific sites. In drug delivery systems, therapeutic agents are encapsulated intracellularly or attached to the surface of the plasma membrane and transported to the desired site. In this review the pros and cons of cell-based therapies are discussed together with their homing mechanisms in the tumor microenvironment. In addition, different strategies to load therapeutic agents inside or on the surface of circulating cells and the current applications for a wide range of disease treatments are summarized.

Although cell-based DDSs have contributed to improving diagnostic and therapeutic effects, there are still many considerations and challenges. First, therapeutic cargo must not cause toxicity to the cell carrier. To prevent this, drugs can be loaded inside vehicles, such as NPs or microparticles, liposomes, and polymers, rather than being freely encapsulated or conjugated with living cells. Second, preserving cell integrity is crucial during surface modifications. Additionally, the process of isolating cells in vivo, loading drugs, and reinjecting them back into the patient has the risk of altering the cell’s original properties. Third, cell-based DDSs face a gap between the theoretical mechanism and practical in vivo outcomes compared to traditional DDSs.

Scheme of living cell-based drug delivery systems.

Choi A, Javius-Jones K, Hong S, Park H. Cell-Based Drug Delivery Systems with Innate Homing Capability as a Novel Nanocarrier Platform. Int J Nanomedicine. 2023;18:509-525

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