scholarly journals MicroRNA delivery mediated by PEGylated polyethylenimine for prostate cancer therapy

2018 ◽  
Vol 16 (1) ◽  
pp. 1257-1267 ◽  
Author(s):  
Chen CY ◽  
Li GY ◽  
Zhang L ◽  
Huang XH ◽  
Cheng D ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zeta Potential ◽  
Transfection Efficiency ◽  
Cell Uptake ◽  
Uniform Size ◽  
Prostate Cancer Therapy ◽  
Effective Inhibition ◽  
Microrna Delivery

AbstractA microRNA (miRNA) nanomedicine PEG-PEI/miR-221/222 was synthesized based on PEGylated polyethylenimine PEG-PEI and used to transfect prostate cancer cells (PC-3) in vitro. Gel retardation assay confirmed the formation of nanomedicine, of which the zeta potential and particle size were determined by dynamic light scattering. Its cytotoxicity was analyzed by CCK-8 assay-while its transfection efficiency was analyzed by flow cytometry. Cell uptake and intracellular distribution of nanoparticles were evaluated using laser confocal microscopy. RT-PCR and western-blot assays were conducted to verify the regulation of SIRT1 target gene. We found that the properties of the nanocomplexes of miRNA and PEG-PEI depended on N/P ratios. At higher N/P ratio, accompanied by higher zeta potential and higher cytotoxicity, PEG-PEI is needed to completely condense the miRNA into small particles with uniform size distribution. Under an N/P ratio of 20, high transfection efficiency and low carrier cytotoxicity were obtained simultaneously in PC-3 cells in vitro. Consequently, the SIRT1 expression was up-regulated due to the nanoparticle-delivered miR-221/222, which resulted in effective inhibition of PC-3 cells. Our study revealed the PEG-PEI/miR-221/222 nanomedicine as a prospective alternative for treatment of advanced prostate cancer and also lays a foundation for future in vivo investigation.

scholarly journals Heavy atom-free semiconducting polymer with high singlet oxygen quantum yield for prostate cancer synergistic phototherapy

2019 ◽  
Vol 3 (6) ◽  
pp. 1123-1127 ◽  
Author(s):  
Jian Shen ◽  
Jianjiao Chen ◽  
Zhen Ke ◽  
Dengfeng Zou ◽  
Liguo Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Therapy ◽  
Quantum Yield ◽  
Singlet Oxygen ◽  
Heavy Atom ◽  
Semiconducting Polymer ◽  
Prostate Cancer Therapy

Heavy atom free NDNT have a great potential for prostate cancer therapy both in vitro and in vivo.

scholarly journals Development of EphA2 siRNA-loaded lipid nanoparticles and combination with a small-molecule histone demethylase inhibitor in prostate cancer cells and tumor spheroids

2020 ◽  
Author(s):  
Ezgi Oner ◽  
Mustafa Kotmakci ◽  
Anne-Marie Baird ◽  
Steven G. Gray ◽  
Bilge Debelec Butuner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cellular Uptake ◽  
Transfection Efficiency ◽  
Cationic Lipid ◽  
Lipid Nanoparticles ◽  
In Vivo Studies ◽  
Great Promise ◽  
Tumor Spheroids

Abstract Background: siRNAs hold a great potential for cancer therapy, however, poor stability in body fluids and low cellular uptake limit their use in the clinic. To enhance the bioavailability of siRNAs in tumors, novel, safe, and effective carriers are needed. Results: Here, we developed cationic solid lipid nanoparticles (cSLNs) to carry siRNAs targeting EphA2 receptor tyrosine kinase (siEphA2), which is overexpressed in many solid tumors including prostate cancer (PCa). Using DDAB cationic lipid instead of DOTMA reduced nanoparticle size and enhanced both cellular uptake and gene silencing in PCa cells. DDAB-cSLN showed better cellular uptake efficiency with similar silencing compared to commercial transfection reagent Dharmafect-2. After verifying the efficacy of siEphA2-loaded nanoparticles, we further evaluated a potential combination with a histone lysine demethylase inhibitor, JIB-04. Silencing EphA2 by siEphA2-loaded DDAB-cSLN did not affect the viability (2D and 3D), migration, and clonogenicity of PC-3 cells alone. However, upon co-administration, there was a decrease in the aforementioned cellular responses due to JIB-04. Furthermore, JIB-04 decreased EphA2 expression, and thus, silencing efficiency of siEphA2-loaded nanoparticles was further increased with co-treatment. Conclusions: We have successfully developed a novel siRNA-loaded lipid nanoparticle for targeting EphA2. Moreover, detailed preliminary results of the effects of JIB-04, alone and in combination with siEphA2, on PCa cells and tumor spheroids were presented for the first time. Our delivery system provides high transfection efficiency and shows a great promise for targeting other genes and cancer types in further in vitro and in vivo studies.

scholarly journals Development of EphA2 siRNA-loaded lipid nanoparticles and combination with a small-molecule histone demethylase inhibitor in prostate cancer cells and tumor spheroids

2020 ◽  
Author(s):  
Ezgi Oner ◽  
Mustafa Kotmakci ◽  
Anne-Marie Baird ◽  
Steven G. Gray ◽  
Bilge Debelec Butuner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cellular Uptake ◽  
Transfection Efficiency ◽  
Cationic Lipid ◽  
Lipid Nanoparticles ◽  
Great Promise ◽  
Tumor Spheroids ◽  
Lysine Demethylase

AbstractsiRNAs hold a great potential for cancer therapy, however, poor stability in body fluids and low cellular uptake limit their use in the clinic. To enhance the bioavailability of siRNAs in tumors, novel, safe, and effective carriers are needed. Here, we developed cationic solid lipid nanoparticles (cSLNs) to carry siRNAs targeting EphA2 receptor tyrosine kinase (siEphA2), which is overexpressed in many solid tumors including prostate cancer (PCa). Using DDAB cationic lipid instead of DOTMA reduced nanoparticle size and enhanced both cellular uptake and gene silencing in PCa cells. After verifying the efficacy of siEphA2-loaded nanoparticles, we further evaluated a potential combination with a histone lysine demethylase inhibitor, JIB-04. Silencing EphA2 by siEphA2-loaded DDAB-cSLN did not affect the viability (2D and 3D), migration, and clonogenicity of PC-3 cells alone. However, upon co-administration, there was a decrease in the aforementioned cellular responses due to JIB-04. Furthermore, JIB-04 decreased EphA2 expression, and thus, silencing efficiency of siEphA2-loaded nanoparticles was further increased with co-treatment. In conclusion, we have successfully developed a novel siRNA-loaded lipid nanoparticle for targeting EphA2. Moreover, detailed preliminary results of the effects of JIB-04, alone and in combination with siEphA2, on PCa cells and tumor spheroids were presented for the first time. Our delivery system provides high transfection efficiency and shows a great promise for targeting other genes and cancer types in further in vitro and in vivo studies.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

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