Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Gene Delivery Systems

Background:

• Reversible addition-fragmentation chain transfer (RAFT) polymerization combines advantages of radical and living polymerization.
• Biocompatible block copolymers are crucial for developing effective and safe gene delivery vectors.
• Functionalization of polymers can enhance their interaction with genetic material and cellular uptake.

Purpose of the Study:

• To synthesize methionine-functionalized biocompatible block copolymers via RAFT polymerization.
• To investigate the plasmid DNA (pDNA) complexation capabilities of the synthesized block copolymers.
• To establish a simple and convenient protocol for creating novel gene carrier materials.

Main Methods:

• Synthesis of N,N-bis(2-hydroxyethyl)methacrylamide-b-N-(3-aminopropyl)methacrylamide (BNHEMA-b-APMA) via RAFT polymerization.
• Modification of amine groups in APMA with methionine and guanidine to yield methionine-grafted copolymers (mBG).
• Characterization using ninhydrin reaction for APMA content, gel permeation chromatography (GPC) for molecular weight, and investigation of pDNA complexation via charge ratios, Zeta potential, and particle size analysis.

Main Results:

• Three block copolymers (mBG1, mBG2, mBG3) with varying APMA content (21%, 37%, 52%) were successfully synthesized.
• Synthesized copolymers exhibited controlled molecular weights (16,200-27,200 g/mol) and demonstrated effective pDNA complexation at specific charge ratios (N/P: 4-16).
• Positive Zeta potential was observed for mBG/pDNA polyplexes at N/P ratios > 1, with particle sizes ranging from 100-200 nm at N/P ratios of 16-32.

Conclusions:

• Methionine-functionalized biocompatible block copolymers were successfully prepared using a straightforward RAFT polymerization approach.
• The synthesized copolymers exhibit promising pDNA complexing abilities, indicating their potential as effective gene carriers.
• This study provides a versatile protocol for developing novel block copolymer-based gene delivery systems.