Stimuli‐Responsive Hydrogel Microcapsules Harnessing the COVID‐19 Immune Response for Cancer Therapeutics

Vector-functionalized lentivirus-loaded DNA tetrahedra-modified stimuli-responsive hydrogel microcapsules act as active carriers for gene expression in cancer cells and immunogenetic therapy of cancer cells. This is exemplified by designing Alpha-fetoprotein (AFP)-aptamer or miRNA-responsive carriers, expressing green fluorescence protein and the AFP-stimulated expression of the spike protein, harnessing the COVID-19 immune response for cancer therapy.

Abstract

The combination of gene therapy and immunotherapy concepts, along recent advances in DNA nanotechnology, have the potential to provide important tools for cancer therapies. We present the development of stimuli-responsive microcapsules, loaded with a viral immunogenetic agent, harnessing the immune response against the Coronavirus Disease 2019, COVID-19, to selectively attack liver cancer cells (hepatoma) or recognize breast cancer or hepatoma, by expression of green fluorescence protein, GFP. The pH-responsive microcapsules, modified with DNA-tetrahedra nanostructures, increased hepatoma permeation by 50 %. Incorporation of a GFP-encoding lentivirus vector inside the tumor-targeting pH-stimulated miRNA-triggered and Alpha-fetoprotein-dictated microcapsules enables the demonstration of neoplasm selectivity, with approximately 5,000-, 8,000- and 50,000-fold more expression in the cancerous cells, respectively. The incorporation of the SARS-CoV-2 spike protein in the gene vector promotes specific recognition of the immune-evading hepatoma by the COVID-19-analogous immune response, which leads to cytotoxic and inflammatory activity, mediated by serum components taken from vaccinated or recovered COVID-19 patients, resulting in effective elimination of the hepatoma (>85 % yield).

Zum Volltext