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Topical Delivery of microRNA-125b by Framework Nucleic Acids for Psoriasis Treatment
Yunfeng Han1, Long Xi1,2, Fang Leng3
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, People's Republic of China.
Purpose:
Psoriasis is a chronic and recurrent inflammatory dermatitis characterized by T cell imbalance and abnormal keratinocyte proliferation. MicroRNAs (miRNAs) hold promise as therapeutic agents for this disease; however, their clinical application is hindered by poor stability and limited skin penetration. This study demonstrates the utilization of Framework Nucleic Acid (FNA) for the topical delivery of miRNAs in psoriasis treatment.
Methods:
By utilizing miRNA-125b as the model drug, FNA-miR-125b was synthesized via self-assembly. The successful synthesis and stability of FNA-miR-125b in bovine fetal serum (FBS) were verified through gel electrophoresis. Subsequently, flow cytometry was employed to investigate the cell internalization on HaCaT cells, while qPCR determined the effects of FNA-miR-125b on cellular functions. Additionally, the skin penetration ability of FNA-miR-125b was assessed. Finally, a topical administration study involving FNA-miR-125b cream on imiquimod (IMQ)-induced psoriasis mice was conducted to evaluate its therapeutic efficacy.
Results:
The FNA-miR-125b exhibited excellent stability, efficient cellular internalization, and potent inhibition of keratinocyte proliferation. In the psoriasis mouse model, FNA-miR-125b effectively penetrated the skin tissue, resulting in reduced epidermal thickness and PASI score, as well as decreased levels of inflammatory cytokines.
Insights
Framework Nucleic Acid (FNA) enhances topical delivery of microRNAs (miRNAs) for psoriasis treatment. FNA-miRNA formulations show improved stability, skin penetration, and reduced inflammation in mouse models.
Area of Science:
- Biomaterials Science
- Dermatology
- Molecular Biology
Background:
- Psoriasis is a chronic inflammatory skin disease driven by T cell imbalance and keratinocyte overgrowth.
- MicroRNAs (miRNAs) show therapeutic potential for psoriasis but face challenges in stability and skin penetration.
- Framework Nucleic Acids (FNAs) offer a novel platform for nucleic acid delivery.
Purpose of the Study:
- To develop and evaluate Framework Nucleic Acid-conjugated microRNA-125b (FNA-miR-125b) for topical psoriasis treatment.
- To assess the stability, cellular uptake, and efficacy of FNA-miR-125b.
- To investigate the therapeutic potential of FNA-mediated miRNA delivery in a preclinical psoriasis model.
Main Methods:
- FNA-miR-125b was synthesized and its stability confirmed using gel electrophoresis.
- Cellular internalization and functional effects were analyzed in HaCaT cells via flow cytometry and qPCR.
- Skin penetration and therapeutic efficacy were evaluated in an imiquimod-induced psoriasis mouse model.
Main Results:
- FNA-miR-125b demonstrated high stability and efficient cellular uptake.
- Topical application of FNA-miR-125b cream reduced epidermal thickness and inflammatory markers in mice.
- The formulation effectively inhibited keratinocyte proliferation and improved psoriasis-like symptoms.
Conclusions:
- FNA technology enables effective topical delivery of miRNAs for psoriasis.
- FNA-miR-125b shows significant therapeutic potential by enhancing miRNA stability and skin penetration.
- This approach offers a promising strategy for managing chronic inflammatory skin conditions like psoriasis.
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