Engineered microorganism-based delivery systems for targeted cancer therapy: a narrative review

Abstract

Microorganisms with innate and artificial advantages have been regarded as intelligent drug delivery systems for cancer therapy with the help of engineering technology. Although numerous studies have confirmed the promising prospects of microorganisms in cancer, several problems such as immunogenicity and toxicity should be addressed before further clinical applications. This review aims to investigate the development of engineered microorganism-based delivery systems for targeted cancer therapy. The main types of microorganisms such as bacteria, viruses, fungi, microalgae, and their components and characteristics are introduced in detail. Moreover, the engineering strategies and biomaterials design of microorganisms are further discussed. Most importantly, we discuss the innovative attempts and therapeutic effects of engineered microorganisms in cancer. Taken together, engineered microorganism-based delivery systems hold tremendous promise for biomedical applications in targeted cancer therapy.

Keywords: drug delivery systems; engineering strategies; microorganisms; targeted cancer therapy.

Figure 1. Schematic diagram of microorganism-based delivery systems for targeted cancer therapy.

Figure 2. Representative examples of (A) physical integration strategies via electrostatic interactions, (B) chemical engineering strategies via covalent conjugation, (C) biological engineering strategies via genetic editing, and (D) cell membrane coating strategy. Scale bars: 1 μm. Ce6: chlorin e6; DOX: doxorubicin; E. Coli: Escherichia coli; E. Coli(p): Escherichia coli with a plasmid expressing the catalase; E. faecalis: Enterococcus faecalis; Ec-PR848: PR848 nanoparticle-load E. Coli; LP: liposome; MTB: magnetotactic bacteria; pDA: polydopamine; PDOX: DOX-loaded PLGA nanoparticles; PLGA: poly(lactic-co-glycolic acid); S. aureus: Staphylococcus aureus. A was reprinted with permission from Wei et al. Copyright 2021 American Chemical Society. B was reprinted with permission from Taherkhani et al. Copyright 2014 American Chemical Society. C was reprinted from Deng et al. Copyright 2021, with permission from Elsevier Ltd. D was reprinted from Cao et al.

Figure 3. Two applications of bacteria in cancer chemotherapy. Reprinted from Cao and Liu. Copyright 2020 Elsevier B.V.

Figure 4. The modulatory mechanisms of the immune cells in the tumour microenvironment by fungal β-glucan. DC: dendritic cell; GrnzB: granzyme B; INF-γ: interferon-γ; M-MDSC: monocytic myeloid-derived suppressor cell; PMNMDSC: polymorphonuclear myeloid-derived suppressor cell; ROS: reactive oxygen species; TNF-α: tumor necrosis factor-α; WGP: whole-glucan particles. Reprinted from Geller et al.

Figure 5. Anti-tumour effects of chlorella extracts and lutein on human colon cancer cells. Reprinted with permission from Cha et al. Copyright 2008 American Chemical Society.

Figure 6. (A) Intratumoral inoculation of OV with transfection and immune cell recruitment. (B) Advanced transfection of an oncolytic virus into the tumour and niche cells with induction of immune cells resulting in apoptosis, direct cell lysis, niche disruption, and phagocytosis. (C) Distant tumour immune infiltration is induced by local immune conditioning. Blue: immune cells; red: tumour; orange: OV particles; green: tumour niche. OV: oncolytic virus. Reprinted from Raja et al.