Glycogen for Smyd3-antisense oligonucleotide delivery and enhanced liver cancer gene therapy

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Gene Therapy

Background:

• Smyd3 overexpression is linked to various cancers, particularly liver cancer, making it a therapeutic target.
• Antisense oligonucleotides (ASOs) show promise for silencing Smyd3 mRNA but face challenges in stability and cellular delivery.
• Existing strategies for ASO delivery, like chemical modifications and synthetic nanocarriers, raise safety concerns.

Purpose of the Study:

• To develop and evaluate a novel glyco-nanovector for efficient delivery of Smyd3-ASOs.
• To assess the biocompatibility, stability, and cellular uptake enhancement of the nanovector.
• To investigate the therapeutic efficacy of the nanovector-ASO complex in inhibiting liver cancer cell proliferation.

Main Methods:

• Synthesis of aminated glycogen (NG) nanovector by grafting glycogen with diethylenetriamine (DETA).
• Complexation of NG with Smyd3-ASOs to form NG/ASOs and evaluation of their stability and cellular uptake in HepG2 cells.
• Assessment of Smyd3 protein translation inhibition and HepG2 cell proliferation following NG/ASO treatment.

Main Results:

• Aminated glycogen (NG) demonstrated good biocompatibility and efficiently complexed with Smyd3-ASOs, protecting them from degradation.
• NG significantly enhanced the cellular uptake of Smyd3-ASOs in HepG2 liver cancer cells.
• The NG/ASO complex effectively reduced Smyd3 protein levels and inhibited HepG2 cell proliferation.

Conclusions:

• Glycogen-based nanovectors offer an efficient and potentially safer platform for ASO delivery in cancer gene therapy.
• The developed glyco-nanovector shows significant potential for Smyd3-targeted liver cancer treatment.
• This study highlights the promise of utilizing glycogen's inherent nanostructure for therapeutic applications.