Tumor Microenvironment-Responsive Magnetotactic Bacteria-Based Multi-Drug Delivery Platform for MRI-Visualized Tumor Photothermal Chemodynamic Therapy

Simple Summary Cancer cells display elevated reactive oxygen species (ROS) and an altered redox status. For this study, taking advantage of these characteristics, we designed a multifunctional MRI-visualizable multi-drug delivery platform, AMB@PDAP-Fe (APPF), based on magnetotactic bacteria (AMB) for MRI-visualized tumor photo-thermotherapy (PTT) and enhanced chemodynamic therapy (CDT). Upon magnetic navigation, APPF accumulated in the tumor microenvironment. The PDAP-Fe in the composite was reduced by glutathione (GSH) in the tumor microenvironment and produced Fe2+, which catalyzed the generation of reactive oxygen species (ROS) through the Fenton reaction and induced tumor cell apoptosis. The magnetosomes in AMB displayed good dual-mode contrast capability in an MRI, which was later used to visualize the process of tumor treatment. Upon NIR light irradiation, the magnetosomes in magnetotactic bacteria immediately converted the light energy into heat energy and the tumor tissue was heated up, thus causing the death of tumor cells. It is noteworthy that the heat generated during the synergistic PTT process (to which PDAP partly contributed) accelerated the releasing of Fe2+ from PDAP-Fe, which enhanced the catalytic conversion of endogenous H2O2 into <middle dot>OH, and, thus, achieved synergistic photothermal-enhanced Fenton-reaction-mediated cancer therapy. This study demonstrates the feasibility of developing an MRI-visualizable multi-drug delivery platform from magnetic bacteria, which, compared with other manmade inorganic multi-drug delivery platforms, are lively, self-propelled, and magnetically navigated. This study also highlights the synergistic tumor-curing effect between magnetic bacteria and PDAP-Fe and the importance of understanding the underlying cooperative molecular mechanism between different drugs when scheduling combination therapy.Abstract Cancer cells display elevated reactive oxygen species (ROS) and altered redox status. Herein, based on these characteristics, we present a multi-drug delivery platform, AMB@PDAP-Fe (APPF), from the magnetotactic bacterium AMB-1 and realize MRI-visualized tumor-microenvironment-responsive photothermal-chemodynamic therapy. The Fe3+ in PDAP-Fe is reduced by the GSH at the tumor site and is released in the form of highly active Fe2+, which catalyzes the generation of ROS through the Fenton reaction and inhibits tumor growth. At the same time, the significant absorption of the mineralized magnetosomes in AMB-1 cells in the NIR region enables them to efficiently convert near-infrared light into heat energy for photothermal therapy (PTT), to which PDAP also contributes. The heat generated in the PTT process accelerates the process of Fe2+ release, thereby achieving an enhanced Fenton reaction in the tumor microenvironment. In addition, the magnetosomes in AMB-1 are used as an MRI contrast agent, and the curing process is visualized. This tumor microenvironment-responsive MTB-based multi-drug delivery platform displays the potency to combat tumors and demonstrates the utility and practicality of understanding the cooperative molecular mechanism when designing multi-drug combination therapies.