Chemoenzymatic surface decoration of Nisin-shelled nanoemulsions: Novel targeted drug-nanocarriers for cancer applications

Rania A Hashad; Ritu Singla; Sukhvir Kaur Bhangu; Edwina Jap; Haiyan Zhu; Anton Y Peleg; Luke Blakeway; Christoph E Hagemeyer; Francesca Cavalieri; Muthupandian Ashokkumar; Karen Alt

doi:10.1016/j.ultsonch.2022.106183

Chemoenzymatic surface decoration of Nisin-shelled nanoemulsions: Novel targeted drug-nanocarriers for cancer applications

Ultrason Sonochem. 2022 Nov:90:106183. doi: 10.1016/j.ultsonch.2022.106183. Epub 2022 Sep 28.

Authors

Affiliations

¹ NanoTheranostics Laboratory, Australian Center for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia; NanoBiotechnology Laboratory, Australian Center for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, AinShamsUniversity, Cairo, Egypt.
² School of Chemistry, University of Melbourne, VIC 3010, Australia.
³ NanoTheranostics Laboratory, Australian Center for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
⁴ School of Chemistry, University of Melbourne, VIC 3010, Australia; School of Science, RMIT University, Melbourne, VIC 3000, Australia.
⁵ Department of Infectious Diseases, The Alfred Hospital & Monash University, VIC 3004, Australia.
⁶ NanoBiotechnology Laboratory, Australian Center for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia.
⁷ School of Science, RMIT University, Melbourne, VIC 3000, Australia.
⁸ NanoTheranostics Laboratory, Australian Center for Blood Diseases, Monash University, Melbourne, VIC 3004, Australia. Electronic address: karen.alt@monash.edu.

Abstract

Nisin, a peptide used as a natural food preservative, is employed in this work for the development of a novel nanocarrier system. Stable and uniform nisin-shelled nanoemulsions (NSNE) with a diameter of 100 ± 20 nm were successfully prepared using 20 kHz flow-through ultrasonication technique. The NSNE showed limited toxicity, high bactericidal activity and high drug loading capacity (EE 65 % w/w). In addition, the nisin shell was exploited for the site-specific attachment of a recombinantly produced cancer targeting ligand (αHER2_LPETG IgG). Employing a unique two phases (bio-click) approach which involved both Sortase A mediated Azide Bioconjugation (SMAB) and Strain Promoted Azide Alkyne Cycloaddition (SPAAC) reactions, targeted NSNE (NSNE_DOX-αHER2 IgG) were successfully assembled and loaded with the chemotherapeutic drug Doxorubicin (DOX). Finally, NSNE_DOX-αHER2 IgG showed cancer-specific binding and augmented cytotoxicity to HER2 expressing tumour cells.

Keywords: Drug delivery; Nanoemulsion; Nisin; Ultrasonication.

MeSH terms

Azides
Doxorubicin / pharmacology
Humans
Immunoglobulin G
Neoplasms*
Nisin* / pharmacology

Substances

Azides
Nisin
Doxorubicin
Immunoglobulin G