Design of curdlan-based pH-sensitive polymers with endosome buffering functionality for siRNA delivery

Area of Science:

• Biomaterials Science
• Gene Therapy
• Nanotechnology

Background:

• Synthetic small interfering RNAs (siRNAs) are promising therapeutic agents for gene expression control but require efficient delivery systems due to poor membrane permeability.
• Current transmembrane siRNA delivery technologies often face challenges with biocompatibility and efficacy.

Purpose of the Study:

• To develop a biocompatible siRNA delivery agent using chemically modified curdlan polymers.
• To evaluate the siRNA binding, cytotoxicity, buffering capacity, and transfection efficiency of novel curdlan-based polymers (Curimi).

Main Methods:

• Curdlan derivative 6AC-100 was chemically modified to introduce imidazole rings, creating Curimi polymers.
• Curimi polymers were characterized for their ability to form nanoparticles with siRNA, including size and zeta potential at varying pH.
• Cytotoxicity, endosome buffering capacity, and siRNA transfection efficiency were assessed in cancer cells using siRNA targeting PLK1 mRNA.

Main Results:

• Curimi polymers formed stable siRNA nanoparticles (85-105 nm) at pH 7.4, with size and zeta potential sensitive to pH changes.
• Curimi exhibited lower cytotoxicity and enhanced buffering capacity compared to the parent 6AC-100.
• Efficient delivery of siRNA targeting PLK1 was achieved, leading to significant inhibition of target mRNA levels in cancer cells.

Conclusions:

• Novel curdlan-based Curimi polymers demonstrate potential as effective and biocompatible siRNA carriers.
• These Curimi polymers show promise for advancing siRNA-based cancer gene therapy by facilitating intracellular delivery and gene silencing.