Tailor-made oligonucleotide-loaded lipid-polymer nanosystems designed for bone gene therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Gene therapy offers potential for treating systemic metabolic disorders like osteoporosis (OP).
• Developing efficient delivery vehicles for genetic material to target cells remains a significant challenge.
• Nanosystem internalization pathways are influenced by surface properties and cell type.

Purpose of the Study:

• To create PEGylated lipid-PLGA nanoparticles (NPs) with tunable surface charges for incorporating GapmeRs (single-strand antisense oligonucleotides).
• To evaluate these nanoparticles as a potential gene therapy strategy for osteoporosis treatment.

Main Methods:

• Synthesized PEGylated lipid-PLGA nanoparticles with varying surface charges (negative, positive, neutral) by adjusting lipid composition.
• Incorporated GapmeRs into the nanoparticles, assessing encapsulation efficiency and loading independence of surface charge.
• Investigated the internalization of these nanoparticles by mesenchymal stem cells (MSCs).

Main Results:

• Achieved nanoparticles with low polydispersity index and suitable size.
• Demonstrated high encapsulation efficiency for GapmeRs, with loading unaffected by surface charge.
• Confirmed adequate internalization of all NP formulations by MSCs.

Conclusions:

• Developed a versatile portfolio of surface-modified nanoparticles for gene therapy applications.
• These nanoparticles effectively encapsulate GapmeRs and are internalized by MSCs.
• Further studies will explore the impact of NP surface charge on intracellular distribution and gene therapy efficacy in OP.