An injectable cell penetrable nano-polyplex hydrogel for localized siRNA delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Targeted delivery of small interfering RNA (siRNA) is crucial for effective gene silencing.
• Existing delivery systems often face challenges with efficiency, duration, and site-specificity.
• Developing localized and sustained release systems for nucleic acid therapeutics is an ongoing need.

Purpose of the Study:

• To develop a cell-penetrable nano-polyplex assembled hydrogel for localized siRNA delivery.
• To evaluate the long-term gene silencing efficiency and localized effect of the developed system.
• To leverage the thermosensitive properties of poly(organo-phosphazene) for sustained release.

Main Methods:

• Preparation of a hydrogel by conjugating protamine to poly(organo-phosphazene) and forming nano-polyplexes with siRNAs.
• In vivo administration of the thermosensitive hydrogel solution, which self-assembles into a gel.
• Monitoring the release of 30 nm nano-polyplexes and assessing gene silencing efficacy at the target site.

Main Results:

• The hydrogel system demonstrated sustained release of nano-polyplexes for up to 4 weeks.
• The released nano-polyplexes exhibited efficient cell penetration, leading to effective siRNA delivery.
• High gene silencing efficiency was achieved specifically at the target site following a single injection.

Conclusions:

• The cell-penetrable nano-polyplex assembled hydrogel system offers a promising approach for localized and long-term siRNA delivery.
• The thermosensitive nature of the hydrogel enables sustained release and enhanced therapeutic outcomes.
• This innovative system holds potential for advancing targeted gene therapy applications.