EpCAM aptamer activated 5-FU-loaded PLGA nanoparticles in CRC treatment; in vitro and in vivo study
In this study, epithelial cell adhesion molecule (EpCAM) aptamer-activated nanoparticles (Ap-NPs) were synthesised to enhance treatment efficiency in colorectal cancer (CRC). PLGA [poly(d, l-lactide-co-glycolide)] copolymer was fabricated by conjugation of COOH-PEG-NH2 to PLGA-COOH through an EDC/NHS-mediated chemistry. Afterwards, 5-fluorouracil-loaded (FU) nanoparticles were prepared using the water/oil/water double emulsion solvent evaporation method. The in vitro cytotoxicity of formulations was evaluated using the MTT assay in HCT-116, CT-26 and HEK-293 cell lines. For in vivo study, tumour-bearing BALB/c mice were established by subcutaneous injection of CT-26 cell line. The results indicated that fabricated AP-FU-NPs had 101 nm size with a spherical surface, relatively homogeneously and, satisfactory encapsulation efficiency (83.93%). In vitro experiments revealed that Ap-FU-NPs had a superior in vitro cytotoxicity than both FU-NPs and free 5-FU in CT-26 and HCT-116 cells but, were significantly low toxic against HEK-293 cells relative to free 5-FU. Furthermore, in vivo results showed no significant haemolytic effect, hepatic and renal injury, or weight loss. After treatment of various animal groups with formulations, notable tumour growth delay was observed following the order: Ap-FU-NPs < FU-NPs < 5-FU < PBS. The results suggest that AP-FU-NPs could be an effective and promising carrier for 5-FU delivery to the EpCAM overexpressing CRC cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Journal of drug targeting - 31(2023), 3 vom: 18. März, Seite 296-309 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yavari, Bahram [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.02.2023 Date Revised 03.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/1061186X.2022.2148679 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM349117497 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a In this study, epithelial cell adhesion molecule (EpCAM) aptamer-activated nanoparticles (Ap-NPs) were synthesised to enhance treatment efficiency in colorectal cancer (CRC). PLGA [poly(d, l-lactide-co-glycolide)] copolymer was fabricated by conjugation of COOH-PEG-NH2 to PLGA-COOH through an EDC/NHS-mediated chemistry. Afterwards, 5-fluorouracil-loaded (FU) nanoparticles were prepared using the water/oil/water double emulsion solvent evaporation method. The in vitro cytotoxicity of formulations was evaluated using the MTT assay in HCT-116, CT-26 and HEK-293 cell lines. For in vivo study, tumour-bearing BALB/c mice were established by subcutaneous injection of CT-26 cell line. The results indicated that fabricated AP-FU-NPs had 101 nm size with a spherical surface, relatively homogeneously and, satisfactory encapsulation efficiency (83.93%). In vitro experiments revealed that Ap-FU-NPs had a superior in vitro cytotoxicity than both FU-NPs and free 5-FU in CT-26 and HCT-116 cells but, were significantly low toxic against HEK-293 cells relative to free 5-FU. Furthermore, in vivo results showed no significant haemolytic effect, hepatic and renal injury, or weight loss. After treatment of various animal groups with formulations, notable tumour growth delay was observed following the order: Ap-FU-NPs < FU-NPs < 5-FU < PBS. The results suggest that AP-FU-NPs could be an effective and promising carrier for 5-FU delivery to the EpCAM overexpressing CRC cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 5-Fluorouracil | |
| 650 | 4 | |a EpCAM aptamer | |
| 650 | 4 | |a PLGA nanoparticles | |
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| 700 | 1 | |a Jalali, Akram |e verfasserin |4 aut | |
| 700 | 1 | |a Najafi, Rezvan |e verfasserin |4 aut | |
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