Bioengineered immunomodulatory organelle targeted nanozymes for photodynamic immunometabolic therapy

Abstract

Intelligent nanomedicines integrated with stimuli-responsive components enable on-demand customizable treatment options which would improve therapeutic outcome and reduce systemic toxicity. In this work, we explore the synergistic therapeutic potential of photodynamic therapy and immunometabolic modulation to achieve tumour regression and to trigger an adaptive immunity to prevent tumour recurrence. The therapeutic potential of the fabricated Bioengineered Immunomodulatory Organelle targeted Nanozymes (BIONs) was tested on 3D printed mini-brains which could effectively recapitulate the biologically relevant interactions between glioblastoma cells and macrophages. In the presence of glioblastoma organotypic brain slices, activated BIONs upregulated the cell surface expression of CD86, a costimulatory molecule and CD83, maturation marker, on monocyte derived dendritic cells, suggesting its ability to elicit a strong immune response. Furthermore, the antigen pulsed dendritic cells by chemotaxis and transendothelial migration readily relocate into the draining lymph node where they present the antigenic cargo to enable the proliferation of T lymphocytes. The stealth and tunable catalytic activity of BIONs prevent ROS mediated diseases such as acute kidney injury by providing environment dependent protection without compromising on its promising anti-cancer activity.

Keywords: 3D bioprinted mini-brain; Acute kidney injury; Glioblastoma organotypic brain slices; Photodynamic immunometabolic therapy; Stealth; Stimuli responsive.