Table 1. Biological carriers in the development of a bacterial robot.

Biological carrier

Features and benefits

Example

A living bacterium

Ability to move independently towards a target; autonomous existence in different physiological conditions; possibility of genetic modifications; metabolically active.

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Minicells

High immunogenicity; significant load capacity; inability to reproduce; decreased metabolic activity.

Mini-cells obtained from the E. coli Nissle 1917 strain and loaded with doxorubicin target breast tumor cells in mice using the pHLIP protein brought to the surface [124];

Mini-cells based on the E. coli Nissle 1917 strain, producing the therapeutic protein azurin, have been developed for the treatment of colorectal cancer [125].

Outer membrane vesicles (OMV)

High immunogenicity; ability to deliver cargo inside the target cell

On the surface of OMVs (from E. coli) loaded with miRNA, urease is immobilized through a biotin-streptavidin coupling, which metabolizes bioavailable urea, thereby setting the nanobiorobot in motion, while the surface of the vesicles is provided with CPP-peptide for better targeting of tumor cells [126];

OMVs derived from Salmonella enterica induce activation of the immune system, inhibit the growth of tumor cells, and can be used as a vector for the delivery of therapeutic agents [127];

OMVs from the attenuated Klebsiella pneumonia strain loaded with doxorubicin effectively penetrated NSCLC A549 cells and inhibited tumor growth in mice [128].

Bacterial ghosts

High immunogenicity; significant load capacity; inability to reproduce; lack of metabolic activity.

The "bacterial ghost" from E. coli is loaded with the antitumor drug 5-fluorouracil and tested for cytotoxicity on the CACO2 cell line [129]:

The "bacterial ghost" from the E. coli strain ATCC 25922 is loaded with paclitaxel and sequentially encapsulated with several layers of the cancer cell membrane for better internalization in the treatment of metastatic lung cancer [130]

Bacterial dormant spores

Resistance to environment; non-toxicity; the ability to activate and germinate inside the tumor; the possibility of genetic modifications in the vegetative stage.

Gold nanorods are attached to the surface of Bacillus subtilis spores, which can heat up when irradiated in the near infrared range. The hyperthermic effect on tumor tissue is enhanced by the potential germination of spores into an active vegetative form and the competition of dividing bacteria for nutrients with cancer cells [131].

Magnetosomes

Sensitivity to external magnetic field; non-toxic.

Magnetosomes modified with human serum albumin and chemically conjugated with fluorescently labeled antibodies against epidermal growth factor receptors were used to visualize breast tumors in mice using MRI [132];

Magnetosomes used to deliver plasmids carrying the cecropin B (ABPs) and apoptin (VP3) genes to human hepatocellular carcinoma (HepG2) cells significantly increased transfection efficiency compared with lipofectamine, and also inhibited tumor growth in the mouse model [133].