Pathogen-mimicking nanocomplexes: self-stimulating oxidative stress in tumor microenvironment for chemo-immunotherapy

Abstract

A novel drug-loaded pathogen-mimicking nanocomplex has been constructed for synergistic chemo-immunotherapy using detoxified lipopolysaccharide coated mesoporous silica nanoparticle. Detoxified lipopolysaccharide behaves as a dual-purpose entity that not only effectively mimics the function of the natural pathogen for triggering immune responses but also acts as a lid for inhibiting premature chemical drug release. In this approach, a knock-on effect would be observed at site of tumor: firstly, pathogen-mimicries elicited the elevated production of ROS; secondly, excessive production of ROS in turn oxidized the arylboronic ester to realize controlled chemotherapy; thirdly, in addition to inducing ROS generation, the nanocomplex would self-stimulate macrophages activation which subsequently activated cytotoxic T cells. Importantly, chemotherapy and immunotherapy were acting in a synergistic manner to inhibit solid tumor growth. Moreover, chemotherapeutic agents could be effectively released upon exposure to self-stimulating oxidative stress in which external addition of ROS was avoided. This proof of concept might open the door to a new generation of carrier materials in the field of cancer therapy.