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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

Schematic illustration of the fabrication of siRNA-loaded PEAL NPs.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; W1, internal water phase; O, oil phase; W2, external water phase.
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f1-ijn-10-5447: Schematic illustration of the fabrication of siRNA-loaded PEAL NPs.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; W1, internal water phase; O, oil phase; W2, external water phase.

Mentions: In this study, we selected PEAL as the nanocarrier. The emulsification-solvent evaporation method is shown in Figure 1. The cationic polymer can form NPs, and the siRNA is entrapped within the NP via ionic interactions and not by simple adsorption onto the surface,13 therefore, siRNA could be immobilized in the formed NPs at high EE. Furthermore, the outer layer of siRNA-loaded PEAL NPs was covered with mPEG, which could improve the stability of the NPs due to its hydrophilicity and excellent biocompatibility.26,27


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)

Schematic illustration of the fabrication of siRNA-loaded PEAL NPs.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; W1, internal water phase; O, oil phase; W2, external water phase.
© Copyright Policy
Related In: Results  -  Collection

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

f1-ijn-10-5447: Schematic illustration of the fabrication of siRNA-loaded PEAL NPs.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; W1, internal water phase; O, oil phase; W2, external water phase.
Mentions: In this study, we selected PEAL as the nanocarrier. The emulsification-solvent evaporation method is shown in Figure 1. The cationic polymer can form NPs, and the siRNA is entrapped within the NP via ionic interactions and not by simple adsorption onto the surface,13 therefore, siRNA could be immobilized in the formed NPs at high EE. Furthermore, the outer layer of siRNA-loaded PEAL NPs was covered with mPEG, which could improve the stability of the NPs due to its hydrophilicity and excellent biocompatibility.26,27

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