Magnetotactic Bacteria-Based Drug-Loaded Micromotors for Highly Efficient Magnetic and Biological Double-Targeted Tumor Therapy.

Bacteria-mediated cancer therapy has attracted much attention in recent years. However, using magnetotactic bacteria as both a drug carrier and a drug for cancer therapy has never been reported. Herein, we incorporated a photosensitizer chlorin e6 (Ce6) into the M. magneticum strain AMB-1 through a chemical bond or physical blending. A chemical reaction was finally selected for fabricating AMB-1/Ce6 micromotors, as such micromotors exhibited high drug payload and normal bacterial activities. An interesting finding is that AMB-1 is not only an excellent drug carrier but also a unique drug that could inhibit mouse tumor growth. We also, for the first time, demonstrated that AMB-1 is a photosensitizer. Under laser irradiation, micromotors killed cancer cells with high efficiency due to the high-level reactive oxygen species generated by the micromotors. Micromotors could target the hypoxic and normoxic regions in vitro via both the active swimming of AMB-1 and external magnetic field guidance. Micromotors showed high tumor-homing ability owing to the above double targeting mechanisms. After injection with the micromotors followed by magnetic field guidance and laser irradiation, the growth of mouse tumors was significantly inhibited owing to the AMB-1-based biotherapy and phototoxicity of AMB-1 and Ce6. This micromotor-mediated tumor-targeted therapy strategy may be a great platform for treating many types of solid tumors.

Low frequency vibrating magnetic field-triggered magnetic microspheres with a nanoflagellum-like surface for cancer therapy.

BACKGROUND: The magneto-mechanical force killing cancer cells is an interesting and important strategy for cancer therapy. RESULTS: Novel magnetic microspheres composed of a Fe3O4 nanocore, a bovine serum albumin (BSA) matrix, and a rod-like SiO2 nanoshell, which had flagellum-like surface for force-mediated cancer therapy were developed. One such magnetic microsphere (Fe3O4/BSA/rSiO2) at a cancer cell (not leave the cell surface) under a low frequency vibrating magnetic field (VMF) could generate 6.17 pN force. Interestingly, this force could induce cancer cell to generate reactive oxygen species (ROS). The force and force-induced ROS could kill cancer cells. The cell killing efficiency of Fe3O4/BSA/rSiO2 exposed to a VMF was enhanced with increasing silica nanorod length, and the microspheres with straight nanorods exhibited stronger cell killing ability than those with curled nanorods. Fe3O4/BSA/rSiO2 triggered by a VMF could efficiently inhibit mouse tumor growth, while these microspheres without a VMF had no significant effect on the cell cycle distribution, cell viability, tumor growth, and mouse health. CONCLUSIONS: These microspheres with unique morphological characteristics under VMF have great potential that can provide a new platform for treating solid tumors at superficial positions whether with hypoxia regions or multidrug resistance.

Nanodrug-loaded Bifidobacterium bifidum conjugated with anti-death receptor antibody for tumor-targeted photodynamic and sonodynamic synergistic therapy.

Using bacteria for tumor-targeted therapy has attracted much attention in recent years. However, how to improve the targeted delivery and cancer therapy efficacy is an important but challenging scientific issue. Herein, a drug delivery system using a probiotic as a carrier was developed for tumor-targeted photodynamic and sonodynamic synergistic therapy. In this system, chlorin e6 (Ce6) nanoparticles (NPs) were prepared and incorporated into B. bifidum, followed by the conjugation of anti-death receptor 5 antibody (anti-DR5 Ab). Interestingly, B. bifidum under 671 nm laser or ultrasound (US) irradiation could generate reactive oxygen species (ROS), and Ce6-B. bifidum-anti-DR5 Ab obtained could target hypoxic regions in tumor with high efficiency after intravenous injection. The ROS level generated by Ce6-B. bifidum-anti-DR5 Ab under both laser and US irradiation was much higher than the combined ROS generated separately using a laser and US for the same probiotics. The cytotoxicity and laryngeal tumor growth-inhibiting efficiency of Ce6-B. bifidum-anti-DR5 Ab under both laser and US irradiation were significant higher than the values obtained using laser or US irradiation alone, which demonstrated the synergistic effect on tumor growth. B. bifidum could be eliminated from the body without exerting harmful effects on mouse health. This strategy is a platform that can be extended to treat other solid tumors. STATEMENT OF SIGNIFICANCE: Using bacteria as drug delivery carriers will show unique advantages. However, how to improve the targeted delivery efficiency and tumor inhibiting capacity is a challenging scientific issue. Herein, a delivery system using a probiotic as carrier was developed for tumor-targeted therapy. In this delivery system, chlorin e6 nanoparticles were prepared and then incorporated into living Bifidobacterium bifidum (B.bifidum), followed by the conjugation of anti-death receptor 5 antibody. This delivery system could efficiently target to mouse tumors, accumulate the hypoxic areas and inhibit the tumor growth through the photodynamic and sonodynamic synergistic effect. Our results will provide a platform for B.bifidum-mediated tumor targeted therapy.