E. coli as a Smart Thermo-Vector for Combating Solid Tumors: A Synergistic Heat-Induced Cancer Therapy Approach.

Abstract

Heat-induced cancer therapies such as magnetic hyperthermia-based cancer therapy (MHCT) and photothermal tumor ablation (PTT) have garnered significant attention as minimally invasive new-generation cancer therapy modalities. However, solid tumors associated with hypoxia present a considerable challenge to effective cancer therapy. In this study, we took up the challenge of mitigating the limiting penetration ability of nanoparticles by integrating polydopamine-coated magnetic nanoparticles and motile anaerobic bacteria (PDBs) to function as a smart thermo-vector. The developed PDBs are capable of self-navigating hypoxic tumors and as thermo-therapy agents with the ability to induce heat through exposure to an alternating magnetic field or near-infrared laser light. The thermo-vector system exhibited a dual-functioning synergistic antitumor effect of MHCT and PTT and an outstanding tumor targeting efficiency, outperforming the conventional 'nanoparticles only' approach. The heat-induced cellular oxidative stress and disrupted mitochondrial function led to 80% cellular cytotoxicity within 24 h of treatment. The PDB-based approach led to complete tumor regression in c57BL/6 mice within 21 days of treatment and a tumor-free survival for 60 days without recurrence, proving the capability of the developed PDBs in combatting solid tumors.