Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles

Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer.

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Targeted delivery and apoptosis induction of trans-resveratrol-ferulic acid loaded chitosan coated folic acid conjugate solid lipid nanoparticles in colon cancer cells

Carbohydrate Polymers ◽

10.1016/j.carbpol.2019.115682 ◽

2020 ◽

Vol 231 ◽

pp. 115682 ◽

Cited By ~ 12

Author(s):

Chinnaiyan Senthil Kumar ◽

Ramar Thangam ◽

Soloman Agnes Mary ◽

Perumal Ramesh Kannan ◽

Gopinath Arun ◽

...

Keyword(s):

Colon Cancer ◽

Folic Acid ◽

Ferulic Acid ◽

Cancer Cells ◽

Targeted Delivery ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Apoptosis Induction ◽

Colon Cancer Cells ◽

Acid Conjugate

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Targeted Delivery of siRNA to Ovarian Cancer Cells Using Functionalized Graphene Oxide

Nano LIFE ◽

10.1142/s1793984418500010 ◽

2018 ◽

Vol 08 (01) ◽

pp. 1850001 ◽

Cited By ~ 1

Author(s):

Shibin Du ◽

Yunfei Wang ◽

Junping Ao ◽

Kai Wang ◽

Zhiying Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Graphene Oxide ◽

Gene Delivery ◽

Cancer Cells ◽

Targeted Delivery ◽

Small Interfering Rna ◽

Folate Receptor ◽

Ovarian Cancer Cells ◽

Functionalized Graphene Oxide ◽

Interfering Rna

Ovarian cancer is the highest mortality rate of all cancers in the female reproductive system. Over the past decades, small interfering RNA (si RNA) has been explored as a promising therapeutic candidate for gene therapy. However, its clinical application is limited by the lack of safe and efficient methods for gene delivery. Graphene oxide (GO) was modified with polyethylene glycol (PEG), polyethylenimine (PEI) and folic acid (FA), for targeted delivery of small interfering RNA (siRNA) that inhibits ovarian cancer cell growth, and the efficacy of such complex was evaluated by a series of in vitro experiments. The synthesized vehicle PEG-GO-PEI-FA was characterized by atomic force microscopy (AFM), Malvern particle size analyzer, UV-visible spectroscopy and Fourier transform infrared spectroscopy (FTIR), and the results showed that PEG, PEI and FA could be covalently grafted to GO surface, forming PEG-GO-PEI-FA particles with a size of [Formula: see text][Formula: see text]nm and a potential of 14.7[Formula: see text]mV. Agarose-gel electrophoresis demonstrated that siRNA can be adsorbed onto the surface of PEG-GO-PEI-FA by electrostatic interaction. Laser confocal microscopy demonstrated that siRNA-adsorbed PEG-GO-PEI-FA could be target into folate receptor (FR)-overexpressing ovarian cancer cells. Compared to the PEG-GO-PEI/siRNA without folate modification, PEG-GO-PEI-FA/siRNA showed more pronounced inhibitory effect on growth of ovarian cancer cells. In conclusion, we have successfully synthesized a vector that is safe, efficient and specific to target tumor cell for gene delivery.

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NEAT1 siRNA Packed with Chitosan Nanoparticles Regulates the Development of Colon Cancer Cells via lncRNA NEAT1/miR-377-3p Axis

BioMed Research International ◽

10.1155/2021/5528982 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Tianyu Li ◽

Nenghui Deng ◽

Ruimei Xu ◽

Zhihao Fan ◽

Junli He ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Chitosan Nanoparticles ◽

Luciferase Reporter ◽

Colon Cancer Cells ◽

Potential Binding ◽

The Impact ◽

Lncrna Neat1 ◽

Great Inhibition

This study was for verifying that transfecting colon cancer cells (CCCs) with lncRNA NEAT1 packed with siRNA chitosan nanoparticles (CNPs) can suppress lncRNA NEAT1 and biological behaviors of the cells. siRNA targeting lncRNA NEAT1 expression vector was constructed and then transfected into CCCs after being packed with CNPs. Subsequently, the impact of the transfection on biological behaviors of the cells was evaluated. As a result, with high expression in CCCs, NEAT1 was negatively bound up with miR-377-3p in cases with colon cancer (CC), and dual luciferase reporter assay confirmed the potential binding region. Additionally, after downregulating NEAT1 in CCCs, transfection of NEAT1 siRNA packed with CNPs brought a great inhibition on cell proliferation and a promotion on apoptosis, and inhibiting miR-377-3p was able to offset the role of silencing NEAT1 in CCCs. Therefore, in our opinion, NEAT1 siRNA packed with CNPs can hinder the growth and metastasis of CCCs by knocking down NEAT1 in CC, and its mechanism may be achieved by targeting miR-377-3p, which offers a novel direction for treating CC.

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Folic Acid Conjugated PEG-PCL-PEG Triblock Copolymer Nanoparticles for Enhanced Delivery of 5-Fluorouracil to HT29 Colon Cancer Cells

10.21203/rs.3.rs-58920/v1 ◽

2020 ◽

Author(s):

Parvin Sadat Mirzaghavami ◽

Samideh Khoei ◽

Sepideh Khoee ◽

Sakine Shirvalilou

Keyword(s):

Colon Cancer ◽

Folic Acid ◽

Cancer Cells ◽

Targeted Delivery ◽

Colony Formation ◽

Triblock Copolymer ◽

Therapeutic Index ◽

Ros Production ◽

Colon Cancer Cells ◽

Antitumor Effects

Abstract Background: In the current study, folic acid conjugated magnetite PEG-PCL-PEG triblock copolymer were synthesized and loaded with 5-Fluorouracil (5-FU-SPION-PEG-PCL-PEG-FA) for targeted delivery of drug to HT29 colon cancer cells.Methods: The cytotoxic effect and cellular uptake of synthesized nanoparticles was assessed on HUVEC and HT29 cell lines. In addition, antitumor effects of nanoparticles were investigated based on gene expression of Bax and Bcl2, Annexin V/PI staining, ROS production and colony formation.Results: As compared to 5-FU, an improvement in therapeutic index was demonstrated for 5-FU-SPION-PEG-PCL-PEG-FA according to cytotoxicity induced in HUVEC and HT29 cells. In addition, 5-FU-SPION-PEG-PCL-PEG-FA was found to be more antitumor efficient in comparison to 5-FU based on Bax/Bcl2 ratio, percentage of cell death, ROS production and colony formation ability (P<0.05).Conclusion: The obtained results suggested that 5-FU-SPION-PEG-PCL-PEG-FA could be considered as promising targeted drug delivery system.

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