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Retroductal Nanoparticle Injection to the Murine Submandibular Gland
Published on: May 3, 2018
Anti-tumor effects in mice induced by survivin-targeted siRNA delivered through polysaccharide nanoparticles
Feifei Yang1, Wei Huang, Yunfei Li
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Abstract:
Recently, survivin has been attracting great attention because it plays an important role in inhibiting the apoptosis process of tumor cells. Down-regulating the expression of survivin gene by small interfering RNA (siRNA) offers a promising method for anti-tumor therapy. However, lack of appropriate siRNA delivery vector has significantly hindered the successful application of survivin-targeted siRNA in anti-tumor therapy. The purpose of this study was to use polysaccharide vector TAT-g-CS we synthesized to deliver functional siRNA and evaluate its in vivo anti-tumor activity. TAT-g-CS vector was firstly synthesized and well structurally characterized. MTT assay showed that TAT-g-CS vector exhibited good biocompatibility. TAT-g-CS complexed with siRNA offering nanoparticles with an average particle size of 212.2 nm and a polydispersity index of 0.121, and the zeta potential of the nanoparticles was +18.58 mV. Results from reporter gene assay suggested that luciferase-targeted siRNA when delivered by TAT-g-CS could down-regulate the expression of luciferase gene with 75.3% reduction. Most importantly, we use siRNA(Sur) targeting survivin gene to assess the in vitro and in vivo delivery capacity of TAT-g-CS and its anti-tumor effects. Our results demonstrated that TAT-g-CS/siRNA(Sur) nanoparticles not only strongly inhibited the in vitro proliferation of 4T1-Luc tumor cells via inducing cell apoptosis, but also effectively inhibited the in vivo growth and metastasis of malignant breast tumor, which suggested that TAT-g-CS/siRNA nanoparticle was a highly efficient non-viral system for siRNA delivery, especially for anti-tumor therapy based on siRNA therapeutics.
Insights
A novel polysaccharide vector, TAT-g-CS, effectively delivers small interfering RNA (siRNA) targeting survivin. This approach inhibits tumor cell growth and metastasis, offering a promising strategy for anti-cancer therapy.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Research
Background:
- Survivin is crucial for tumor cell survival by inhibiting apoptosis.
- Small interfering RNA (siRNA) targeting survivin shows potential for anti-cancer therapy.
- Effective delivery vectors are needed for survivin-targeted siRNA therapeutics.
Purpose of the Study:
- To synthesize and characterize a novel polysaccharide vector, TAT-g-CS.
- To evaluate the efficacy of TAT-g-CS for delivering functional siRNA.
- To assess the in vivo anti-tumor activity of TAT-g-CS/siRNA nanoparticles.
Main Methods:
- Synthesis and structural characterization of TAT-g-CS.
- Biocompatibility assessment using MTT assay.
- Nanoparticle characterization (size, PDI, zeta potential).
- Reporter gene assay to confirm siRNA delivery efficiency.
- In vitro and in vivo evaluation of anti-tumor effects using survivin-targeted siRNA (siRNA(Sur)).
Main Results:
- TAT-g-CS demonstrated good biocompatibility.
- TAT-g-CS/siRNA formed nanoparticles with favorable characteristics (212.2 nm size, 0.121 PDI, +18.58 mV zeta potential).
- Luciferase siRNA delivered by TAT-g-CS reduced gene expression by 75.3%.
- TAT-g-CS/siRNA(Sur) nanoparticles inhibited 4T1-Luc tumor cell proliferation and induced apoptosis in vitro.
- Significant inhibition of in vivo breast tumor growth and metastasis was observed.
Conclusions:
- TAT-g-CS is a biocompatible and efficient non-viral vector for siRNA delivery.
- TAT-g-CS/siRNA nanoparticles show potent anti-tumor activity against breast cancer.
- This system holds promise for developing novel siRNA-based anti-cancer therapeutics.
