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Updated: Mar 13, 2026

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its
Ping Sun1, Wei Huang1, Mingji Jin1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines; Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Abstract:
Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.
Insights
Poly(ethylene glycol)-modified chitosan (PEG-CS) nanoparticles effectively deliver small interfering RNA (siRNA) to cancer cells. This novel vector enhances therapeutic delivery, significantly inhibiting tumor growth and metastasis in preclinical models.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapy
Background:
- Small interfering RNA (siRNA) holds therapeutic potential for cancer but faces challenges in delivery due to degradation.
- Effective and safe vectors are crucial for successful siRNA-based cancer treatments.
Purpose of the Study:
- To synthesize and evaluate poly(ethylene glycol)-modified chitosan (PEG-CS) as a safe and efficient vector for siRNA delivery in cancer therapy.
- To assess the stability, cellular uptake, and antitumor efficacy of PEG-CS/siRNA nanoparticles.
Main Methods:
- Synthesis of PEG-CS nanoparticles for encapsulating siRNA.
- Characterization of nanoparticle stability and particle size.
- In vitro evaluation of cellular uptake and antitumor activity in 4T1 cancer cells.
- In vivo assessment of tumor growth inhibition in a 4T1 xenograft mouse model.
Main Results:
- PEG-CS nanoparticles demonstrated superior structural stability and enhanced cellular uptake of siRNA compared to unmodified chitosan nanoparticles.
- In vitro studies showed significant inhibition of 4T1 tumor cell growth with PEG-CS/siRNA.
- In vivo experiments revealed that PEG-CS/siRNA nanoparticles effectively reduced xenograft tumor growth and metastasis.
Conclusions:
- PEG-CS serves as a safe and efficient vector for siRNA delivery.
- PEG-CS/siRNA nanoparticles show significant potential for reducing tumor growth and preventing metastasis in cancer therapy.
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