β‐Sheet Polyelectrolyte Nanostructures: Design, Self‐Assembly, In Vitro, and In Vivo Biological Activity

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Main Authors: Rahul Nisal, Parshuram Kambale, Sunidhi Singh, Shahidkhan Pathan, Manickam Jayakannan
Format: Artículo Open Access
Published: Wiley 2026
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author Rahul Nisal
Parshuram Kambale
Sunidhi Singh
Shahidkhan Pathan
Manickam Jayakannan
author_facet Rahul Nisal
Parshuram Kambale
Sunidhi Singh
Shahidkhan Pathan
Manickam Jayakannan
Rahul Nisal
Parshuram Kambale
Sunidhi Singh
Shahidkhan Pathan
Manickam Jayakannan
collection Wiley Open Access
contents β‐Sheet Polyelectrolyte Nanostructures: Design, Self‐Assembly, In Vitro, and In Vivo Biological Activity Rahul Nisal Parshuram Kambale Sunidhi Singh Shahidkhan Pathan Manickam Jayakannan Advanced Healthcare Materials ABSTRACT Engineering macromolecular systems having protein‐like intelligence is a challenging task since synthetic strategies required to impart both α‐helical and β‐sheet secondary structures in high molecular weight polypeptides along with polyelectrolyte characteristics in a single system. α‐Helical polypetide polyelectrolytes are well‐established; however, the lack of appropriate synthetic methodologies to high molecular weight β‐sheet polypeptidepolyelectrolytes becomes a bottleneck in the construction of protein‐mimicking synthetic nano‐assemblies. Here, we report one of the first attempts to access β‐sheet polypeptide core‐shell polyelectrolytes based on well‐defined block copolymer strategy and demonstrate their diverse action both in vitro and in vivo. Di‐blockpolypeptidesare devised by constituting the first β‐sheet block from ʟ‐serine residue by steric‐hindrance assisted ring opening polymerization (SHAROP) process and the second block from α‐helical promoting ʟ‐glutamate and ʟ‐lysine residues. Post‐polymerization deprotection has restored them into β‐sheet block core‐shell polyelectrolytes having anionic or cationic charges under physiological pH. These β‐sheet polyelectrolytes are self‐assembled into tiny 30 nm nanoparticles and behave as excellent host for loading and delivering anticancer drug doxorubicin and deep‐tissue penetrable NIR biomarkers. The anionic β‐sheet polyelectrolyte is non‐toxic, non‐hemolytic, and exhibited excellent drug delivery capabilities in the in vitro cancer cell lines and in vivo live animal (mice) model. 10.1002/adhm.71111 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/adhm.71111
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institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
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spellingShingle β‐Sheet Polyelectrolyte Nanostructures: Design, Self‐Assembly, In Vitro, and In Vivo Biological Activity
Rahul Nisal
Parshuram Kambale
Sunidhi Singh
Shahidkhan Pathan
Manickam Jayakannan
Advanced Healthcare Materials
β‐Sheet Polyelectrolyte Nanostructures: Design, Self‐Assembly, In Vitro, and In Vivo Biological Activity Rahul Nisal Parshuram Kambale Sunidhi Singh Shahidkhan Pathan Manickam Jayakannan Advanced Healthcare Materials ABSTRACT Engineering macromolecular systems having protein‐like intelligence is a challenging task since synthetic strategies required to impart both α‐helical and β‐sheet secondary structures in high molecular weight polypeptides along with polyelectrolyte characteristics in a single system. α‐Helical polypetide polyelectrolytes are well‐established; however, the lack of appropriate synthetic methodologies to high molecular weight β‐sheet polypeptidepolyelectrolytes becomes a bottleneck in the construction of protein‐mimicking synthetic nano‐assemblies. Here, we report one of the first attempts to access β‐sheet polypeptide core‐shell polyelectrolytes based on well‐defined block copolymer strategy and demonstrate their diverse action both in vitro and in vivo. Di‐blockpolypeptidesare devised by constituting the first β‐sheet block from ʟ‐serine residue by steric‐hindrance assisted ring opening polymerization (SHAROP) process and the second block from α‐helical promoting ʟ‐glutamate and ʟ‐lysine residues. Post‐polymerization deprotection has restored them into β‐sheet block core‐shell polyelectrolytes having anionic or cationic charges under physiological pH. These β‐sheet polyelectrolytes are self‐assembled into tiny 30 nm nanoparticles and behave as excellent host for loading and delivering anticancer drug doxorubicin and deep‐tissue penetrable NIR biomarkers. The anionic β‐sheet polyelectrolyte is non‐toxic, non‐hemolytic, and exhibited excellent drug delivery capabilities in the in vitro cancer cell lines and in vivo live animal (mice) model. 10.1002/adhm.71111 http://onlinelibrary.wiley.com/termsAndConditions#vor
title β‐Sheet Polyelectrolyte Nanostructures: Design, Self‐Assembly, In Vitro, and In Vivo Biological Activity
topic Advanced Healthcare Materials
url https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.71111