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Updated: May 4, 2026

Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Liposomal siRNA nanocarriers for cancer therapy
Bulent Ozpolat1, Anil K Sood2, Gabriel Lopez-Berestein3
1Departments of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
Small interfering RNAs (siRNA) have recently emerged as a new class of therapeutics with a great potential to revolutionize the treatment of cancer and other diseases. A specifically designed siRNA binds and induces post-transcriptional silencing of target genes (mRNA). Clinical applications of siRNA-based therapeutics have been limited by their rapid degradation, poor cellular uptake, and rapid renal clearance following systemic administration. A variety of synthetic and natural nanoparticles composed of lipids, polymers, and metals have been developed for siRNA delivery, with different efficacy and safety profiles. Liposomal nanoparticles have proven effective in delivering siRNA into tumor tissues by improving stability and bioavailability. While providing high transfection efficiency and a capacity to form complexes with negatively charged siRNA, cationic lipids/liposomes are highly toxic. Negatively charged liposomes, on the other hand, are rapidly cleared from circulation. To overcome these problems we developed highly safe and effective neutral lipid-based nanoliposomes that provide robust gene silencing in tumors following systemic (intravenous) administration. This delivery system demonstrated remarkable antitumor efficacy in various orthotopic human cancer models in animals. Here, we briefly overview this and other lipid-based approaches with preclinical applications in different tumor models for cancer therapy and potential applications as siRNA-nanotherapeutics in human cancers.
Insights
Neutral lipid-based nanoliposomes offer a safe and effective way to deliver small interfering RNAs (siRNA) for cancer therapy. This novel approach demonstrates robust gene silencing and significant antitumor efficacy in preclinical models.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapeutics
Background:
- Small interfering RNAs (siRNA) are a promising therapeutic class for gene silencing in diseases like cancer.
- Current siRNA delivery faces challenges including degradation, poor cellular uptake, and rapid clearance, limiting clinical use.
- Lipid-based nanoparticles are explored for siRNA delivery, but cationic liposomes are toxic and anionic liposomes are cleared quickly.
Purpose of the Study:
- To develop and evaluate safe and effective neutral lipid-based nanoliposomes for systemic siRNA delivery in cancer therapy.
- To demonstrate robust gene silencing and significant antitumor efficacy of the developed nanoliposomes in preclinical cancer models.
Main Methods:
- Development of neutral lipid-based nanoliposomes for siRNA encapsulation and delivery.
- Systemic (intravenous) administration of nanoliposomes in orthotopic human cancer models in animals.
- Assessment of gene silencing efficacy and antitumor activity in various tumor models.
Main Results:
- Neutral lipid-based nanoliposomes demonstrated robust gene silencing in tumors following systemic administration.
- The developed delivery system exhibited remarkable antitumor efficacy across diverse orthotopic human cancer models.
- This approach overcomes the toxicity and clearance issues associated with cationic and anionic liposomes.
Conclusions:
- Neutral lipid-based nanoliposomes represent a highly safe and effective platform for siRNA-based cancer nanotherapeutics.
- This technology holds significant potential for clinical applications in treating human cancers through targeted gene silencing.
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