Multi-arm carriers composed of an antioxidant lignin core and poly(glycidyl methacrylate-co-poly(ethylene glycol)methacrylate) derivative arms for highly efficient gene delivery

Abstract

A lignin-based copolymer with good biocompability was successfully prepared via atom transfer radical polymerization (ATRP) for efficient gene delivery. Kraft lignin was modified into lignin-based macroinitiators and then poly(glycidyl methacrylate)-co-poly(ethylene glycol)methacrylate (PGMA-PEGMA) side chains were prepared via ATRP grafting onto lignin. Ethanolamine was sequentially functionalized onto lignin-PGMA-PEGMA and a cationic lignin-PGEA-PEGMA copolymer consisting of a lignin core and differentlength PGEA-PEGMA side chains was produced. Lignin-PGEA-PEGMA copolymers could efficiently compact pDNA into nanoparticles with sizes ranging from 150 to 250 nm at N/P ratios of 10 or higher. The gene transfection efficiency depends greatly on the mass percentage of PGEA units and the N/P ratio. The lignin-PGEA-PEGMA with 46.9% (mass%) of PGEA units (i.e. LG100) has highest transfection efficiency in comparison with the copolymers with a lower amount of PGEA units. In addition, LG100 has high transfection efficiency under serum conditions, which is comparable to or much higher than PEI control in HEK 293T and Hep G2 cell lines. More importantly, lignin-PGEA-PEGMA copolymers have excellent antioxidant activity. The novel cationic lignin-PGEA-PEGMA copolymers can be promising gene carriers for gene delivery.

Lignin‐based polymers via graft copolymerization

“…(h) Graft‐from ATRP of methyl methacrylate . (i) Graft‐from ATRP of glycidyl methacrylate and PEG methyl ether methacrylate …”

Lignin‐Based Micro‐ and Nanomaterials and their Composites in Biomedical Applications

“…synthesized another multi‐arm copolymer, lignin‐ co ‐poly(glycidyl methacrylate)‐ co ‐poly(ethylene glycol)methacrylate (lignin–PGEA–PEGMA) for gene transfection. The lignin–PGEA–PEGMA with 46.9 % of PGEA units showed better gene transfection efficiency than those with a lower amount of PGEA units, and even better than the commercial agent polyethyleneimine (PEI) …”

Utilising inorganic nanocarriers for gene delivery

“…7 Polymeric, lipid and peptide carriers have been extensively studied in recent years. [9][10][11][12][13][14][15][16][17] Functional inorganic nanomaterials recently emerged as robust and versatile nanoscaffolds for effective gene delivery applications. 5,6 Significantly, without the limitations associated with viral vectors, inorganic nanomaterials further offer an appealing set of properties for practical applications, including scalability in synthesis, facile functionalization, chemical and thermal stability.…”