Systemic delivery of E6/7 siRNA using novel lipidic particles and its application with cisplatin in cervical cancer
S Y Wu1, A Singhania, M Burgess
1Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Australia.
Abstract:
Small interfering RNA (siRNA) shows great promise in cancer therapy, but its effectiveness in vivo still remains a crucial issue for its transition into the clinics. Although the successful use of polyethylene glycol (PEG)ylated lipidic delivery systems have already been reported, most of the formulation procedures used are labour intensive and also result in unstable end products. We have previously developed a simple yet efficient hydration-of-freeze-dried-matrix (HFDM) method to entrap siRNA within lipid particles, in which the products exhibited superior stability. Here, we show that these HFDM-formulated particles are stable in the presence of serum and can deliver siRNA efficiently to tumours after intravenous administration. Using these particles, around 50% knockdown of the target gene expression was observed in tumours. With the use of siRNA targeting the E6/7 oncogenes expressed in cervical cancer, we showed a 50% reduction in tumour size. This level of tumour growth suppression was comparable to that achieved from cisplatin at the clinically used dose. Overall, our results demonstrate the feasibility of using HFDM-formulated particles to systematically administer E6/7-targeted siRNA for cervical cancer treatment. The simplicity of preparation procedure along with superior product stability obtained from our method offers an innovative approach for the in vivo delivery of siRNA.
Insights
This study introduces a simple method for creating stable lipid particles that deliver small interfering RNA (siRNA) effectively to tumors. This approach shows promise for in vivo cancer therapy, including cervical cancer treatment.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Small interfering RNA (siRNA) holds therapeutic potential for cancer but faces challenges in effective in vivo delivery.
- Existing polyethylene glycol (PEG)ylated lipidic delivery systems are often labor-intensive and yield unstable products.
Purpose of the Study:
- To evaluate the stability and efficacy of siRNA-loaded lipid particles prepared using a novel hydration-of-freeze-dried-matrix (HFDM) method.
- To assess the potential of HFDM-formulated siRNA for in vivo cancer treatment, specifically targeting cervical cancer.
Main Methods:
- Formulation of siRNA-loaded lipid particles using the hydration-of-freeze-dried-matrix (HFDM) method.
- Assessment of particle stability in serum and in vivo tumor delivery after intravenous administration.
- Evaluation of gene knockdown and tumor size reduction in a cervical cancer model using siRNA targeting E6/7 oncogenes.
Main Results:
- HFDM-formulated lipid particles demonstrated stability in serum and efficient siRNA delivery to tumors.
- Approximately 50% knockdown of target gene expression was achieved in tumors.
- A 50% reduction in cervical tumor size was observed, comparable to cisplatin treatment.
Conclusions:
- The HFDM method provides a simple and efficient approach for producing stable siRNA-loaded lipid particles for in vivo delivery.
- HFDM-formulated E6/7-targeted siRNA represents a feasible strategy for cervical cancer treatment.
- This method offers an innovative solution for overcoming in vivo siRNA delivery challenges in cancer therapy.
