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

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ezgi Oner ◽  
Mustafa Kotmakci ◽  
Anne-Marie Baird ◽  
Steven G. Gray ◽  
Bilge Debelec Butuner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Transfection Efficiency ◽  
3D Culture ◽  
Lipid Nanoparticles ◽  
In Vivo Studies ◽  
Great Promise ◽  
Prostate Cancer Cells ◽  
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. Using DDAB cationic lipid instead of DOTMA reduced nanoparticle size and enhanced both cellular uptake and gene silencing in prostate cancer 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 or 3D culture), migration, nor clonogenicity of PC-3 cells alone. However, upon co-administration with JIB-04, there was a decrease in cellular responses. Furthermore, JIB-04 decreased EphA2 expression, and thus, silencing by siEphA2-loaded nanoparticles was further increased with co-treatment. Conclusions We have successfully developed a novel siRNA-loaded lipid nanoparticle for targeting EphA2. Moreover, preliminary results of the effects of JIB-04, alone and in combination with siEphA2, on prostate cancer cells and prostate cancer tumor spheroids were presented for the first time. Our delivery system provides high transfection efficiency and shows 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 ◽  
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.

scholarly journals A Review of the Potential of Phytochemicals from Prunus africana (Hook f.) Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Komakech ◽  
Youngmin Kang ◽  
Jun-Hwan Lee ◽  
Francis Omujal
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Treatment Options ◽  
Chemotherapeutic Agents ◽  
Sub Saharan Africa ◽  
In Vivo Studies ◽  
Prostate Cancer Cells ◽  
Prunus Africana

Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

scholarly journals Telomerase Inhibition, Telomere Shortening, and Cellular Uptake of the Perylene Derivatives PM2 and PIPER in Prostate Cancer Cells

2019 ◽  
Vol 42 (6) ◽  
pp. 906-914 ◽  
Author(s):  
Navakoon Kaewtunjai ◽  
Ratasark Summart ◽  
Ariyaphong Wongnoppavich ◽  
Bannakij Lojanapiwat ◽  
T. Randall Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Prostate Cancer Cells ◽  
Telomere Shortening ◽  
Telomerase Inhibition ◽  
Perylene Derivatives

A Resveratrol-Loaded Poly(2-hydroxyethyl methacrylate)-Chitosan Based Nanotherapeutic: Characterization and In Vitro Cytotoxicity Against Prostate Cancer

2021 ◽  
Vol 21 (4) ◽  
pp. 2090-2098
Author(s):  
Erdal Eroglu
Keyword(s):  
Prostate Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Human Prostate ◽  
Great Promise ◽  
Hydroxyethyl Methacrylate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Delivery Efficiency

The delivery of therapeutic molecules such as drugs, nucleic acids, or other active molecules into the target tissue and cells is limited because of biological and cellular barriers. Recently, many efforts are being made to bypass these barriers using nanosized drug delivery vehicles. For the targeted transfer of anticancer agents into the cancer tissue with higher efficiency and lower cellular toxicity, synthesis of nano-scale smart materials hold great promise due to the enhanced permeability and retention capability. Encapsulation of natural anticancer compounds such as resveratrol displaying low water-solubility and poor chemical stability into nanomaterials are intensely being studied to achieve the enhanced anticancer activity. The aim of this study is to investigate the drug delivery efficiency of the poly(2-hydroxyethyl methacrylate) (pHEMA)-chitosan nanoparticles (PCNPs) against PC-3 human prostate cancer cells In Vitro. To achieve this aim, resveratrol (RES), one of the widely known natural anticancer agent, is encapsulated into pHEMA core and pHEMARES nanospheres were coated with a cationic polymer, chitosan. Then, developed PCNPs-RES complexes were characterized using fourier transformed infrared (FTIR) spectroscopy, ultraviolet (UV) visible spectroscopy, scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential and atomic force microscopy (AFM) analyses. The characterization studies revealed the synthesis of PCNPs nanoparticles and the entrapment of RES into PCNPs. Also, the cytotoxicity and drug delivery efficiency of PCNPs-RES complexes were tested in human prostate cancer cells, PC-3, In Vitro. As a consequence, PCNPs was shown to be a promising candidate as a new generation nanotherapeutic against prostate cancer In Vitro.

scholarly journals Delivery of retinoic acid to LNCap human prostate cancer cells using solid lipid nanoparticles

2015 ◽  
Vol 493 (1-2) ◽  
pp. 161-171 ◽  
Author(s):  
Mushfiq H. Akanda ◽  
Rajeev Rai ◽  
Ian J. Slipper ◽  
Babur Z. Chowdhry ◽  
Dimitrios Lamprou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Solid Lipid
Sign in / Sign up

Export Citation Format

Share Document