Targeted APT8(16-34) obtained by cell-SELEX and its internalization with miR-23-5p into activated hepatic stellate...

Area of Science:

• Biochemistry
• Molecular Biology
• Hepatology

Background:

• Hepatic stellate cell activation is central to liver fibrosis pathogenesis.
• Targeting these activated cells is crucial for developing effective anti-fibrotic therapies.
• Current therapeutic strategies lack specific delivery tools for activated hepatic stellate cells.

Purpose of the Study:

• To identify specific aptamers targeting activated hepatic stellate cells.
• To develop a targeted delivery system for anti-fibrotic agents.
• To evaluate the therapeutic potential of aptamer-drug conjugates in liver fibrosis.

Main Methods:

• Systematic evolution of ligands by exponential enrichment (SELEX) on HSC-T6 cell line.
• Aptamer truncation and optimization for enhanced specificity and affinity.
• Conjugation of optimized aptamer (APT8(16-34)) with miR-23b-5p for targeted delivery.

Main Results:

• Eleven aptamer candidates (APT1-11) were identified, with APT8(16-34) showing high specificity for activated hepatic stellate cells in vitro and in vivo.
• APT8(16-34) demonstrated internalization into activated hepatic stellate cells upon conjugation with miR-23b-5p.
• The delivered miR-23b-5p effectively inhibited target mRNA translation, downregulating fibrosis-related proteins.

Conclusions:

• APT8(16-34) is a specific targeting and internalizing agent for activated hepatic stellate cells.
• The APT8(16-34)-miR-23b-5p conjugate facilitates functional delivery of miR-23b-5p into target cells.
• This approach shows promise for developing targeted therapies against liver fibrosis.