Abstract

Heterogeneous cancers are usually recalcitrant to the conventional treatment method involving chemotherapy and radiotherapy. This issue was addressed by development of magnetic hyperthermia therapy (MHT) based on Escherichia coli. To be functional, E. coli was constructed to display the bivalent anti-HER2 affibody (denoted ZH2) on cell surface. The ZH2-displayed strain was further equipped with the biotin-binding motif (AP) which was anchored on the inner leaflet of cell membrane. After permeabilization, the engineered E. coli was loaded with streptavidin-linked magnetic nanoparticles (SiMNPs). The biotinylated AP tethers it to SiMNPs through the biotin-streptavidin interaction. As a result, SiMNPs-loaded E. coli was selectively internalized by HER2-positive cancer cells. Following the application of alternating magnetic field, the viability of cancer cells decreased to 20%. The administration in vivo also significantly caused tumor regression in mice xenografted with human ovarian cancer cells. Overall, this study proposes a new strategy of targeted cancer therapy based on the E. coli-mediated MHT.

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