Limits...
Enhanced delivery of PEAL nanoparticles with ultrasound targeted microbubble destruction mediated siRNA transfection in human MCF-7/S and MCF-7/ADR cells in vitro.

Teng Y, Bai M, Sun Y, Wang Q, Li F, Xing J, Du L, Gong T, Duan Y - Int J Nanomedicine (2015)

Bottom Line: As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations.The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells.Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China ; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

ABSTRACT
The gene knockdown activity of small interfering RNA (siRNA) has led to their use as potential therapeutics for a variety of diseases. However, successful gene therapy requires safe and efficient delivery systems. In this study, we choose mPEG-PLGA-PLL nanoparticles (PEAL NPs) with ultrasound targeted microbubble destruction (UTMD) to efficiently deliver siRNA into cells. An emulsification-solvent evaporation method was used to prepare siRNA-loaded PEAL NPs. The NPs possessed an average size of 132.6±10.3 nm (n=5), with a uniform spherical shape, and had an encapsulation efficiency (EE) of more than 98%. As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations. The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells. Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics.

No MeSH data available.


Related in: MedlinePlus

In vitro cytotoxicity of siRNA and PEAL in MCF-7/S (A–C), MCF-7/ADR (D–F), and L929 cells (G–I). The cells were treated for 24 h (A, D, and G), 48 h (B, E, and H), and 72 h (C, F, and I), respectively.Abbreviations: siRNA, small interfering RNA; PEAL NPs, mPEG-PLGA-PLL nanoparticles; mPEG-PLGA-PLL, monomethoxy polyethylene glycol–polylactic acid/glycolic acid–poly(L-lysine) triblock copolymer; h, hours.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4556292&req=5

f3-ijn-10-5447: In vitro cytotoxicity of siRNA and PEAL in MCF-7/S (A–C), MCF-7/ADR (D–F), and L929 cells (G–I). The cells were treated for 24 h (A, D, and G), 48 h (B, E, and H), and 72 h (C, F, and I), respectively.Abbreviations: siRNA, small interfering RNA; PEAL NPs, mPEG-PLGA-PLL nanoparticles; mPEG-PLGA-PLL, monomethoxy polyethylene glycol–polylactic acid/glycolic acid–poly(L-lysine) triblock copolymer; h, hours.

Mentions: In order to evaluate the in vitro toxicity of siRNA and PEAL, cytotoxicity studies were conducted by using various doses of free siRNA, blank PEAL NPs, and siRNA-loaded PEAL NPs against MCF-7/S, MCF-7/ADR, and L929 cells for 24, 48, and 72 hours. As shown in Figure 3, all groups maintained over 80% cell viability for dosage up to 120 nmol/L within 72 hours, suggesting their good biocompatibility. In addition, a comprehensive evaluation has already been done before to evaluate the safety of PEAL.30 Therefore, the PEAL NPs could be safely used for future studies and in vivo studies.


Enhanced delivery of PEAL nanoparticles with ultrasound targeted microbubble destruction mediated siRNA transfection in human MCF-7/S and MCF-7/ADR cells in vitro.

Teng Y, Bai M, Sun Y, Wang Q, Li F, Xing J, Du L, Gong T, Duan Y - Int J Nanomedicine (2015)

In vitro cytotoxicity of siRNA and PEAL in MCF-7/S (A–C), MCF-7/ADR (D–F), and L929 cells (G–I). The cells were treated for 24 h (A, D, and G), 48 h (B, E, and H), and 72 h (C, F, and I), respectively.Abbreviations: siRNA, small interfering RNA; PEAL NPs, mPEG-PLGA-PLL nanoparticles; mPEG-PLGA-PLL, monomethoxy polyethylene glycol–polylactic acid/glycolic acid–poly(L-lysine) triblock copolymer; h, hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556292&req=5

f3-ijn-10-5447: In vitro cytotoxicity of siRNA and PEAL in MCF-7/S (A–C), MCF-7/ADR (D–F), and L929 cells (G–I). The cells were treated for 24 h (A, D, and G), 48 h (B, E, and H), and 72 h (C, F, and I), respectively.Abbreviations: siRNA, small interfering RNA; PEAL NPs, mPEG-PLGA-PLL nanoparticles; mPEG-PLGA-PLL, monomethoxy polyethylene glycol–polylactic acid/glycolic acid–poly(L-lysine) triblock copolymer; h, hours.
Mentions: In order to evaluate the in vitro toxicity of siRNA and PEAL, cytotoxicity studies were conducted by using various doses of free siRNA, blank PEAL NPs, and siRNA-loaded PEAL NPs against MCF-7/S, MCF-7/ADR, and L929 cells for 24, 48, and 72 hours. As shown in Figure 3, all groups maintained over 80% cell viability for dosage up to 120 nmol/L within 72 hours, suggesting their good biocompatibility. In addition, a comprehensive evaluation has already been done before to evaluate the safety of PEAL.30 Therefore, the PEAL NPs could be safely used for future studies and in vivo studies.

Bottom Line: As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations.The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells.Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People's Republic of China ; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

ABSTRACT
The gene knockdown activity of small interfering RNA (siRNA) has led to their use as potential therapeutics for a variety of diseases. However, successful gene therapy requires safe and efficient delivery systems. In this study, we choose mPEG-PLGA-PLL nanoparticles (PEAL NPs) with ultrasound targeted microbubble destruction (UTMD) to efficiently deliver siRNA into cells. An emulsification-solvent evaporation method was used to prepare siRNA-loaded PEAL NPs. The NPs possessed an average size of 132.6±10.3 nm (n=5), with a uniform spherical shape, and had an encapsulation efficiency (EE) of more than 98%. As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations. The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells. Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics.

No MeSH data available.


Related in: MedlinePlus