Self-propelled And NIR-phototaxis Photosynthetic Bacteria As Photothermal Agents For Hypoxia-targeted Cancer Therapy

The hypoxia region in a solid tumor has been recognized as a complex microenvironment revealing very low oxygen concentration and deficient nutrients.Since the discovery of malignant tumor hypoxia in the solid tumor by Thomlinsons,it has been considered as one of the major causes of tumor radiochemotherapy tolerance,and also a potential source of tumor recurrence and metastasis after tumor treatment.In view of this,more and more attention has been paid to the treatment of tumor in hypoxia region.Although nanocarriers have been developed and shown a better targeting rate to tumor,they still fail to reach the hypoxic regions.Thus,we have attempted to develop hypoxic-targeting agents with self-propelling capability to improve the therapeutic efficiency of tumor.Flagellar bacteria possess self-propelled capability and they can swim in bulk fluid environments in response to physical and chemical cues.Especially,low level of oxygen microenvironment serves as an ideal habitat for a number of the anaerobic and facultative anaerobes and thus including Escherichia coli,Salmonella and Bifidobacterium have been developed for hypoxia-driven cancer therapy and has made breakthrough progress.However,it still faces many problems: most of the anaerobic toxicity is high and needs to be detoxified before application and complicated genetic modification process is needed to introduce therapeutic agents.In addition,the genetic instability cannot be ignored when introduce therapeutic genes into bacteria.In our work,Photosynthetic bacteria(PSB)with the capacities of hypoxic and NIR phototaxis were developed for hypoxia zone-targeted cancer therapy.PSB is facultative anaerobes.The photosynthetic capacitation process is an anaerobic process,so PSB can grow under light and anaerobic conditions.The maximum infrared absorption peaks are about 800 nm and 850 nm and NIR is more favorable to the growth of photosynthetic bacteria,which endows the NIR phototaxis capacity of PSB.Moreover,PSB were nontoxic and widely used for feed additive,which indicated it has no potential virulence and pathogenic effect.More importantly,we found the PSB was capable of converting NIR(808 nm)into heat and thus the PSB themselves could be used as photothermal reagents for eradicating cancer cells which no further complicated post-genetic or drug introduction process were needed.We believe PSB can serve as a new generation of hypoxia-targeted “live drug” and provide a new choice for cancer treatment.