A major problem with cancer therapies is the low specificity of many treatment drugs (Chari, 207; Wadia & Dowdy, 2005). Conventional therapies are often administered in a systemic fashion, leading to numerous unwanted off-target effects. To mitigate such issues, there is thus a need for targeted drug delivery systems for anticancer drugs.
Bacteria have long been considered promising candidates for drug delivery (Patyar et al., 2010). Some strains of bacteria are highly anaerobic, and can only survive in hypoxic environments. As the tumor microenvironment is one of the few hypoxic sites in the human body (Dachs et al., 1997), anaerobic bacteria will therefore thrive in hypoxic tumour cores and die in oxygenated regions, allowing greater specificity in targeting (Malmgern & Flanigan, 1955; Patyar et al., 2010). Clostridium novyi, an anaerobic bacterium, was found to successfully reduce tumour sizes in phase I clinical trials (Patyar et al., 2010). However, Clostridium is relatively more difficult to manipulate than other strains of bacteria, making it an unideal choice of a delivery vector.
Besides strictly anaerobic microbes, there exist other bacteria strains which are facultative anaerobes, the most well-known being Escherichia coli. These strains can survive in both aerobic and anaerobic environments by changing their gene expression programmes accordingly (Salmon, 2013). Thus, we can utilise the natural ability of E. coli to express certain genes under anaerobic conditions to express therapeutic genes or drugs only in the hypoxic core of the tumour.
However, the tumour core is not the only hypoxic location in the body. For example, the bone marrow (Asosingh et al., 2005) and gut are also hypoxic environments in which the anaerobic expression programme may be activated. As a result, there is a need for more specific control of regulation of the therapeutic drugs or genes.
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