Mitochondria-Targeted Polymeric Liposomes for Pre-miRNA Imaging and Gene Therapy.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Molecular Biology

Background:

• Mitochondria-related microRNAs (miRNAs) are crucial for mitochondrial function and disease pathogenesis.
• Challenges exist in delivering nucleic acids to mitochondria for imaging and therapeutic applications.
• Targeted delivery systems are needed to overcome these limitations.

Purpose of the Study:

• To develop pH-responsive liposomes for targeted mitochondrial delivery of nucleic acid probes and therapeutic agents.
• To enable pre-microRNA-34a imaging and miRNA-34a gene therapy in cancer cells.
• To investigate the potential of these liposomes in cancer diagnosis and treatment.

Main Methods:

• Self-assembly of pH-responsive liposomes (R@DA-TPP-SA) encapsulating DNA probes and small interfering RNA (siRNA).
• Mitochondrial targeting facilitated by triphenylphosphine (TPP) modification.
• Intracellular release of DNA probes triggered by acidic pH, leading to hybridization chain reaction (HCR) for fluorescence imaging.
• Lysosomal escape and targeted delivery of siRNA to mitochondria for gene silencing.

Main Results:

• Successful imaging of pre-microRNA-34a in A549 cancer cells with significant fluorescence enhancement.
• Targeted delivery of siRNA to mitochondria, leading to suppressed target gene expression and disrupted mitochondrial membrane potential.
• Induction of cancer cell apoptosis and demonstrated anticancer efficacy both in vitro and in vivo.
• Liposomes exhibited good biocompatibility and low toxicity.

Conclusions:

• The developed pH-responsive liposomes effectively target mitochondria for nucleic acid delivery.
• This system enables simultaneous miRNA imaging and gene therapy for cancer treatment.
• The findings offer a promising platform for diagnosing and treating mitochondrial dysfunction-associated diseases.