Enhancing photodynamic and radionuclide therapy by small interfering RNA (siRNA)-RAD51 transfection via
Ulises Paredes-Hernández1, Leslie V Aguilar-Peña1, Keila Isaac-Olivé1
1Laboratorio de Investigación en Teranóstica, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca, Estado de México, Mexico.
Background Aims:
Gene-silencing by small interfering RNA (siRNA) is an attractive therapy to regulate cancer death, tumor recurrence or metastasis. Because siRNAs are easily degraded, it is necessary to develop transport and delivery systems to achieve efficient tumor targeting. Self-nanoemulsifying systems (SNEDDS) have been successfully used for pDNA transport and delivery, so they may be useful for siRNA. The aim of this work is to introduce siRNA-RAD51 into a SNEDDS prepared with Phospholipon-90G, Labrafil-M1944-CS and Cremophor-RH40 and evaluate its efficacy in preventing homologous recombination of DNA double-strand breaks caused by photodynamic therapy (PDT) and ionizing radiation (IR).
Methods:
The siRNA-RAD51 was loaded into SNEDDS using chitosan. Transfection capacity was estimated by comparison with Lipofectamine-2000.
Results:
SNEDDS(siRNA-RAD51) induced gene silencing effect on the therapies evaluated by cell viability and clonogenic assays using T47D breast cancer cells.
Conclusions:
SNEDDS(siRNA-RAD51) shown to be an effective siRNA-delivery system to decrease cellular resistance in PDT or IR.
Insights
Self-nanoemulsifying systems effectively deliver small interfering RNA (siRNA) targeting RAD51. This approach reduces cancer cell resistance to photodynamic therapy and ionizing radiation treatments.
Area of Science:
- Nanotechnology for drug delivery
- Cancer therapy research
- RNA interference (RNAi) mechanisms
Background:
- Small interfering RNA (siRNA) offers potential for cancer treatment by regulating cancer cell death, recurrence, and metastasis.
- siRNAs are susceptible to degradation, necessitating effective delivery systems for tumor targeting.
- Self-nanoemulsifying drug delivery systems (SNEDDS) have shown promise for nucleic acid delivery and may be suitable for siRNA.
Purpose of the Study:
- To develop and evaluate a SNEDDS formulation for delivering siRNA targeting RAD51 (siRNA-RAD51).
- To assess the efficacy of SNEDDS(siRNA-RAD51) in preventing DNA double-strand break repair via homologous recombination.
- To investigate the potential of this system in combination with photodynamic therapy (PDT) and ionizing radiation (IR) for cancer treatment.
Main Methods:
- siRNA-RAD51 was encapsulated within SNEDDS using chitosan.
- Transfection efficiency was compared against a commercial standard, Lipofectamine-2000.
- The efficacy was evaluated using T47D breast cancer cells through cell viability and clonogenic assays.
Main Results:
- SNEDDS(siRNA-RAD51) demonstrated successful gene silencing of RAD51.
- The system effectively reduced cellular resistance when combined with PDT or IR treatments.
- Cell viability and clonogenic assays confirmed the therapeutic effect in T47D breast cancer cells.
Conclusions:
- SNEDDS serves as an effective delivery system for siRNA-RAD51.
- This formulation can decrease cancer cell resistance to PDT and IR.
- The developed SNEDDS(siRNA-RAD51) holds promise for enhancing cancer therapy outcomes.
