Cationic Hydroxyethyl Cellulose Nanocomplexes and RANK siRNA/Zoledronate Co-Delivery Systems for Osteoclast...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Molecular Biology

Background:

• Osteoclast overactivity contributes to bone diseases.
• Current treatments for osteoclast-related disorders face challenges with siRNA delivery and drug bioavailability.
• Hydroxyethyl cellulose (HEC) modified with polyethylenimine2k (PEI2k) to form HECP2k was investigated.

Purpose of the Study:

• To develop HECP2k-based nanocomplexes for co-delivery of receptor activator of nuclear factor k-B (RANK) siRNA and zoledronate (Zol).
• To evaluate the potential of these nanocomplexes for osteoclast inhibition.
• To overcome limitations of low siRNA transfection efficiency and Zol bioavailability.

Main Methods:

• HECP2k/(RANK siRNA + Zol) nanocomplexes were prepared via simple mixing.
• Characterization included size, zeta potential, and cellular uptake assessment.
• In vitro assays such as tartrate-resistant acid phosphatase (TRAP) assay and qPCR were used to evaluate osteoclast inhibition and gene expression changes.

Main Results:

• Successfully formed nanocomplexes with optimal size (~200 nm) and zeta potential (~20 mV) for cellular uptake.
• Demonstrated high endosomal buffering capacity, suggesting efficient endosomal escape.
• Exhibited low cytotoxicity (>90% cell viability) and superior transfection efficiency compared to PEI25k and HECP2k polyplexes.
• Significantly inhibited TRAP activity (~50%) and modulated osteoclastic gene expression, including a 16-fold increase in FAS gene expression.

Conclusions:

• HECP2k/(RANK siRNA + Zol) nanocomplexes are effective in inhibiting osteoclast differentiation and activity.
• The combinatorial effect of RANK siRNA and Zol induces apoptosis in osteoclasts.
• These nanocomplexes show promise as a therapeutic strategy for bone-related diseases.