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Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo
Published on: February 5, 2019
Guanidine modified polyethyleneimine-g-polyethylene glycol nanocarriers for long interfering RNA (liRNA) based
S Sajeesh1, Jeong Yong Choe, Tae Yeon Lee
1Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University, Suwon 440-746, Republic of Korea. dklee@skku.edu dklee0318@gmail.com.
Abstract:
Combination therapy involving the synergism between different therapeutic approaches seems to be a promising strategy in anticancer treatment. Immunostimulatory long interfering RNA (liRNA) structures capable of executing specific RNA interference (RNAi) mediated gene silencing tasks seem to be potential candidates for a combination approach. Apart from their therapeutic efficacy, the unique structural format of liRNA candidates facilitates better association with cationic polymers and significantly improves their intra-cellular delivery. In this study, we have developed a biocompatible cationic delivery platform based on low molecular weight branched polyethyleneimine-grafted-polyethylene glycol (bPEI-g-PEG) for advanced liRNA based anticancer therapy. With simple guanidine (GU) modification, the bPEI-g-PEG platform could induce a strong RNAi mediated response in cancer cells, without induction of any obvious toxicity. Moreover, liRNA complexed with GU-bPEI-g-PEG which targets expression of Survivin gene sensitized cancer cells for effective chemotherapy. A combination strategy involving immunostimulatory RNAi mediators with conventional chemotherapeutic drugs seems to be an effective approach in advanced anticancer treatment.
Insights
This study developed a guanidine-modified bPEI-g-PEG platform for delivering immunostimulatory long interfering RNA (liRNA) to target Survivin gene expression. This combination therapy enhances cancer cell sensitivity to chemotherapy with minimal toxicity.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapeutics
Background:
- Combination therapy offers synergistic benefits in anticancer treatment.
- Immunostimulatory long interfering RNA (liRNA) shows potential for RNA interference (RNAi) mediated gene silencing.
- liRNA's structure aids complexation with cationic polymers for improved intracellular delivery.
Purpose of the Study:
- To develop a biocompatible cationic delivery platform for liRNA-based anticancer therapy.
- To investigate the efficacy of guanidine (GU) modification on the delivery platform.
- To evaluate the combination of liRNA therapy with chemotherapy.
Main Methods:
- Development of a branched polyethyleneimine-grafted-polyethylene glycol (bPEI-g-PEG) platform.
- Modification of the platform with guanidine (GU).
- Complexation of liRNA with GU-bPEI-g-PEG for targeting Survivin gene expression.
Main Results:
- The GU-bPEI-g-PEG platform demonstrated effective RNAi-mediated gene silencing in cancer cells.
- The platform showed no obvious toxicity.
- liRNA complexed with GU-bPEI-g-PEG sensitized cancer cells to chemotherapy.
Conclusions:
- A GU-modified bPEI-g-PEG platform is effective for liRNA delivery in anticancer therapy.
- This approach shows promise for combination strategies with conventional chemotherapy.
- Immunostimulatory RNAi mediators combined with chemotherapy represent an effective advanced anticancer treatment.
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