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In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment
Published on: March 16, 2018
Tumor Microenvironment-Response Calcium Phosphate Hybrid Nanoparticles Enhanced siRNAs Targeting Tumors InVivo
Abstract:
Short interfering RNA (siRNA)-based therapy has a high potential for application in cancer gene therapy. However, delivery of siRNA to target cells is limited by many factors such as serum ribonuclease (RNase) degradation, off-target effects, and inadequate cellular uptake. In this study, an enzyme-response PEG/Lipids/calcium phosphate hybrid delivery system was constructed for siRNA. The nearly neutral charged siRNA@NP2 was resistant to serum-induced degradation. Compared with the non-enzyme-response siRNA@NP1, siRNA@NP2 had efficient delivery in both SMMC-7721 cell lines and SMMC-7721-bearing nude mice. Moreover, safety evaluation of the nanoparticles revealed that they had no significant toxicity both in vitro and in vivo. The developed siRNA@NP2 delivery system presents an efficient tool for siRNA-based cancer gene therapy in vivo.
Insights
This study developed an enzyme-responsive nanoparticle system for delivering short interfering RNA (siRNA) in cancer gene therapy. The novel siRNA@NP2 system effectively protects siRNA from degradation and enhances cellular uptake, showing promise for in vivo applications.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Gene Therapy
Background:
- Short interfering RNA (siRNA) holds great promise for cancer gene therapy.
- Current limitations include serum degradation, off-target effects, and poor cellular uptake of siRNA.
Purpose of the Study:
- To develop an enzyme-responsive hybrid delivery system for siRNA to overcome delivery challenges.
- To evaluate the efficacy and safety of the novel siRNA delivery system in vitro and in vivo.
Main Methods:
- Construction of an enzyme-responsive PEG/Lipids/calcium phosphate hybrid nanoparticle system (siRNA@NP2).
- Assessment of serum-induced degradation resistance and cellular uptake efficiency.
- Evaluation of in vitro and in vivo delivery in SMMC-7721 cell lines and tumor-bearing nude mice.
Main Results:
- The siRNA@NP2 system demonstrated resistance to serum-induced degradation.
- siRNA@NP2 exhibited efficient delivery in both cell lines and in vivo models.
- Safety evaluations confirmed no significant toxicity of the nanoparticles in vitro and in vivo.
Conclusions:
- The developed enzyme-responsive nanoparticle system (siRNA@NP2) is an effective tool for siRNA delivery in cancer gene therapy.
- This system overcomes key limitations of siRNA delivery, paving the way for improved in vivo therapeutic strategies.
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