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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

Preparation and characterizations of the NPs.Notes: (A) Particle size and size distribution of siRNA-loaded PEAL NPs. (B) TEM image of siRNA-loaded PEAL NPs. (C) Stability of the NPs in PBS (pH 7.4, 0.01 M). (D) Cumulative released rate of siRNA from nanoparticles. Data are represented as means ± SD, n=3.Abbreviations: PDI, polydispersity index; 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; TEM, transmission electron microscopy; PBS, phosphate buffer saline; h, hours.
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f2-ijn-10-5447: Preparation and characterizations of the NPs.Notes: (A) Particle size and size distribution of siRNA-loaded PEAL NPs. (B) TEM image of siRNA-loaded PEAL NPs. (C) Stability of the NPs in PBS (pH 7.4, 0.01 M). (D) Cumulative released rate of siRNA from nanoparticles. Data are represented as means ± SD, n=3.Abbreviations: PDI, polydispersity index; 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; TEM, transmission electron microscopy; PBS, phosphate buffer saline; h, hours.

Mentions: As summarized in Table 2, the ζ potentials of siRNA-loaded PEAL NPs were found to be negatively correlated with the amount of siRNA in feed. Recent data show that NPs carrying a very slight positive charge can penetrate throughout large tumors following systemic administration.28 Additionally, based on the EE and DL, NP1.0 was used for subsequent experiments. The average hydrodynamic diameter (Figure 2A) and the TEM image (Figure 2B) showed that NP1.0 possessed a spherical nanostructure with no aggregation and dispersed well. To investigate the stability of the NPs, the NPs were incubated in PBS (0.01 M, pH =7.4) at 37°C and the average size of NPs was monitored subsequently for 96 hours. As shown in Figure 2C, the size of NPs remained constant during the whole incubation period, especially within 12 hours incubation. The results demonstrated that the hydrated shell formed by mPEG could enhance the hydrophilicity of the NPs and keep them stable at least for 96 hours.


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)

Preparation and characterizations of the NPs.Notes: (A) Particle size and size distribution of siRNA-loaded PEAL NPs. (B) TEM image of siRNA-loaded PEAL NPs. (C) Stability of the NPs in PBS (pH 7.4, 0.01 M). (D) Cumulative released rate of siRNA from nanoparticles. Data are represented as means ± SD, n=3.Abbreviations: PDI, polydispersity index; 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; TEM, transmission electron microscopy; PBS, phosphate buffer saline; h, hours.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-10-5447: Preparation and characterizations of the NPs.Notes: (A) Particle size and size distribution of siRNA-loaded PEAL NPs. (B) TEM image of siRNA-loaded PEAL NPs. (C) Stability of the NPs in PBS (pH 7.4, 0.01 M). (D) Cumulative released rate of siRNA from nanoparticles. Data are represented as means ± SD, n=3.Abbreviations: PDI, polydispersity index; 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; TEM, transmission electron microscopy; PBS, phosphate buffer saline; h, hours.
Mentions: As summarized in Table 2, the ζ potentials of siRNA-loaded PEAL NPs were found to be negatively correlated with the amount of siRNA in feed. Recent data show that NPs carrying a very slight positive charge can penetrate throughout large tumors following systemic administration.28 Additionally, based on the EE and DL, NP1.0 was used for subsequent experiments. The average hydrodynamic diameter (Figure 2A) and the TEM image (Figure 2B) showed that NP1.0 possessed a spherical nanostructure with no aggregation and dispersed well. To investigate the stability of the NPs, the NPs were incubated in PBS (0.01 M, pH =7.4) at 37°C and the average size of NPs was monitored subsequently for 96 hours. As shown in Figure 2C, the size of NPs remained constant during the whole incubation period, especially within 12 hours incubation. The results demonstrated that the hydrated shell formed by mPEG could enhance the hydrophilicity of the NPs and keep them stable at least for 96 hours.

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