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Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Targeted and Efficient Delivery of siRNA Using Tunable Polymeric Hybrid Micelles for Tumor Therapy
Fei Hao1, Shiyan Dong1, Chunmiao Yang1
1School of Life Sciences, Jilin University, Changchun, P.R. China.
Background/Aim:
Effective and targeted delivery of siRNA to tumor cells is a prerequisite to achieving their therapeutic effects. Survivin is up-regulated in tumor cells and is associated with resistance to therapy. Therefore, siRNA-mediated silencing of survivin is a potential therapeutic strategy for cancer. The aim of the study was to examine whether polymeric hybrid micelles can be used to effectively deliver siRNAs into cells.
Materials And Methods:
First, linoleic acid (LA) was conjugated to polyethylenimine (PEI) and methoxy-polyethyleneglycol (mPEG) and two amphiphilic polymers (PEI-LA and mPEG-LA) were obtained. Polymeric hybrid micelle (PHM) was then prepared and characterized by self-assembly of PEI-LA and mPEG-LA at different percentages of the two amphiphilic polymers. A PHM/siRNA complex with optimized composition and good biocompatibility was then prepared and its cellular uptake, biodistribution, and antitumor effects were investigated.
Results:
Survivin siRNA was efficiently delivered to the cells. It reduced survivin protein expression and greatly suppressed tumor growth. Moreover, siRNA loaded in PHM gathered in a solid tumor in mice and achieved an improved anticancer effect compared to naked siRNA.
Conclusion:
PHM is a promising and safe vehicle for siRNA delivery and may find utility in cancer therapy.
Insights
Polymeric hybrid micelles (PHM) effectively deliver survivin siRNA to tumor cells, suppressing tumor growth and enhancing cancer therapy. This safe delivery vehicle shows promise for future therapeutic applications.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapeutics
Background:
- Survivin is upregulated in tumors, contributing to therapy resistance.
- Targeted siRNA delivery to tumor cells is crucial for cancer treatment.
- Survivin silencing via siRNA is a potential anti-cancer strategy.
Purpose of the Study:
- To evaluate polymeric hybrid micelles (PHM) as a delivery system for survivin siRNA.
- To assess the efficacy of PHM-mediated siRNA delivery in cancer cells and tumor models.
Main Methods:
- Synthesized amphiphilic polymers (PEI-LA, mPEG-LA) by conjugating linoleic acid (LA) to PEI and mPEG.
- Prepared and characterized PHM by self-assembly of PEI-LA and mPEG-LA.
- Formulated and evaluated PHM/siRNA complexes for cellular uptake, biodistribution, and anti-tumor effects.
Main Results:
- Survivin siRNA was efficiently delivered into cells using PHM.
- PHM-delivered siRNA reduced survivin protein expression and suppressed tumor growth.
- siRNA loaded in PHM showed improved anti-cancer effects in mice compared to naked siRNA.
Conclusions:
- PHM serves as a promising and safe vehicle for siRNA delivery.
- PHM-based siRNA delivery holds potential for effective cancer therapy.
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