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

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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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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