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

Author:

Fischer Amit1ORCID,Ehrlich Avner2ORCID,Plotkin Yevgeni34ORCID,Ouyang Yu1ORCID,Asulin Klil2,Konstantinos Ioannidis2,Fan Chunhai5,Nahmias Yaakov2,Willner Itamar1ORCID

Affiliation:

1. Institute of Chemistry, The Minerva Center for Bio-hybrid Complex Systems The Hebrew University of Jerusalem Jerusalem 91904 Israel

2. Grass Center for Bioengineering, Benin School of Computer Science and Engineering The Hebrew University of Jerusalem Jerusalem 91904 Israel

3. The Department of Anesthesiology, Critical Care and Pain Medicine Hadassah University Hospital Jerusalem 9112001 Israel

4. Faculty of Medicine Hebrew University of Jerusalem Jerusalem 9112001 (Israel)

5. School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine Shanghai Jiao Tong University Shanghai 200240 China

Abstract

AbstractThe 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).

Publisher

Wiley

Subject

General Medicine

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