Targeted delivery of anti-miR-155 by functionalized mesoporous silica nanoparticles for colorectal cancer therapy

Area of Science:

• Oncology
• Nanotechnology
• Molecular Biology

Background:

• MicroRNA-155 (miR-155) is an oncogenic microRNA frequently overexpressed in colorectal cancer (CRC).
• Targeting miR-155 offers a potential therapeutic strategy for CRC, but effective delivery remains a challenge.
• Nuclear factor kappa B (NF-κB) is implicated in cancer pathways and its relationship with miR-155 in CRC requires further investigation.

Purpose of the Study:

• To investigate the expression of miR-155 and NF-κB in CRC and their relationship.
• To develop and evaluate a novel targeted nanoformulation for delivering anti-miR-155 therapy in CRC.
• To assess the therapeutic efficacy and chemosensitizing potential of the developed nanoformulation.

Main Methods:

• Exploration of miR-155 and NF-κB expression and their correlation in CRC tissues and cell lines.
• Development of anti-miR-155 loaded mesoporous silica nanoparticles (MSNs) functionalized with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt).
• In vitro and in vivo evaluation of the nanoformulation's targeting efficiency, miR-155 downregulation, and therapeutic effects in SW480 CRC cells.

Main Results:

• A positive feedback loop was identified between NF-κB and miR-155 in CRC.
• MSNs-anti-miR-155@PDA-Apt demonstrated efficient delivery and significant downregulation of miR-155 in SW480 cells.
• The nanoformulation exhibited enhanced therapeutic effects in vitro and in vivo, and improved sensitivity to 5-fluorouracil chemotherapy.

Conclusions:

• The developed MSNs-anti-miR-155@PDA-Apt nanoformulation is a promising strategy for targeted colorectal cancer therapy.
• Targeting the miR-155/NF-κB axis presents a viable approach for enhancing CRC treatment outcomes.
• This nanoformulation holds potential for improving the efficacy of existing chemotherapy regimens.