Versatile RNA interference nanoplatform for systemic delivery of RNAs

Area of Science:

• Biomedical Engineering
• Nanotechnology
• RNA Therapeutics

Background:

• Developing effective, non-toxic RNA delivery systems for cancer therapy is challenging.
• Current RNAi therapeutics face hurdles in stability, targeting, and cellular uptake.
• Tumor-specific delivery and overcoming drug resistance are critical for clinical success.

Purpose of the Study:

• To engineer a versatile nanoplatform for targeted delivery of RNA interference (RNAi) and small-molecule drugs.
• To create a pH-responsive nanoparticle system for enhanced therapeutic efficacy.
• To evaluate the potential of this nanoplatform in treating drug-resistant cancers.

Main Methods:

• Fabrication of a hyaluronic acid nanoparticle with a calcium phosphate coating, incorporating a Zn(II)-DPA artificial RNA receptor.
• Encapsulation of small-molecule drugs (e.g., doxorubicin) and various RNA molecules (siRNA, miRNA).
• In vitro and in vivo evaluation of the nanoplatform's delivery efficiency, gene silencing, and therapeutic effects in cancer models.

Main Results:

• The nanoplatform demonstrated efficient encapsulation and strong binding of RNA molecules.
• Successful in vitro gene silencing and miRNA replacement in human cancer cells.
• In vivo tumor targeting and suppression of tumor growth in drug-resistant cancer models when co-loaded with doxorubicin and siRNA.
• Sensitization of drug-resistant cells to doxorubicin.

Conclusions:

• The developed nanoplatform is a versatile and effective nonviral system for co-delivering chemo- and RNAi therapeutics.
• This approach holds significant potential for overcoming multidrug resistance in cancer treatment.
• The tumor-targeted, pH-responsive nanoformulations offer a promising strategy for advanced RNAi therapeutics.