Transmembrane TNFα-Expressed Macrophage Membrane-Coated Chitosan Nanoparticles as Cancer Therapeutics

[Image: see text] Transmembrane TNFα, a crucial signaling cytokine, holds anticell proliferative potential. Successful delivery of this intact transmembrane protein to the target site is quite intriguing. Amidst numerous nanocarriers, a novel class of new generation macrophage membrane-coated nanocarriers is endowed with innate tumor homing abilities and inherent capacity of escaping body’s defense machinery. In this perspective, a novel therapeutic module has been fabricated by coating a nontoxic, biodegradable chitosan nanoparticle core with engineered macrophage membrane-tethered TNFα. Herein, the expression of membrane-bound TNFα was induced by challenging phorbol 12-myristate 13-acetate-differentiated THP-1 cells with bacterial lipopolysaccharide. Subsequently, the as-synthesized chitosan nanoparticle core was coated with a TNFα-expressed macrophage membrane through an extrusion process. While transmission electron microscopy imaging, sodium dodecyl sulphate polyacrylamide gel electrophoresis, and western blotting results demonstrated successful coating of the chitosan nanoparticles with the TNFα-induced membrane, the cell viability assays on several cancer cells such as—HeLa, MDA-MB-231, and MCF-7 revealed significant innate anticell proliferative potential of these membrane-coated nanoparticles. Additionally, evaluation of expression of several interleukins after treatment demonstrated excellent biocompatibility of the membrane-coated nanoparticles. The fabricated nanoparticles also demonstrated a dose-dependent cell death in tumor spheroids, which was further corroborated with calcein AM/propidium iodide dual staining results. Translation of the therapeutic efficacy of the synthesized nanoparticles from monolayers to tumor spheroids augments its potential in cancer therapy.