Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026
[Preparation of retinoic acid and irinotecan co-loaded lipo-somes and their in vitro evaluation against anaplastic thyroid carcinoma].
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Lyu Shixu, Zhou Yili, Xu Yi, Yang Fan
Аннотация
OBJECTIVES: To prepare retinoic acid (RA) and irinotecan (IRI) co‑loaded liposomes (RA-IRI@Lip) and evaluate their in vitro therapeutic effects against anaplastic thyroid carcinoma (ATC) and their ability to eliminate cancer stem cells (CSCs).
METHODS: RA-IRI@Lip was obtained through the co-encapsulation of RA and IRI within liposomes, using the thin-film hydration method. The particle size, Zeta potential, encapsulation efficiency, and in vitro release profiles of RA-IRI@Lip were characterized. Hemolysis assay was conducted to evaluate blood compatibility. Cellular uptake of FITC-labeled liposomes was assessed. The in vitro anti-ATC effects were evaluated by cell counting kit-8 (CCK‑8), calcein‑AM/PI staining, and Transwell assay. The synergistic effect of RA and IRI was analyzed using the combination index, while flow cytometry was performed to detect the proportions of aldehyde dehydrogenase-positive cells and CD133-positive cells.
RESULTS: The prepared RA-IRI@Lip had an average particle size of (210.3±5.2) nm, a polydispersity index less than 0.3, and Zeta potential of －(13.7±2.3) mV. The encapsulation efficiencies of RA and IRI were (88.1±2.9)% and (86.8±1.6)%, respectively. In vitro release studies showed that RA-IRI@Lip significantly delayed the release of both RA and IRI, with 48-h cumulative release rates of (66.2±3.6)% and (77.7±4.1)%, respectively. Hemolysis assays demonstrated that all tested concentrations of RA-IRI@Lip exhibited hemolysis rates below 3%, indicating good hemocompatibility. Liposomes can be efficiently taken up by ATC cells after FITC labeling. CCK-8 and calcein-AM/PI staining demonstrated that RA-IRI@Lip significantly inhibited the viability of ATC cells and promoted cell death, with an IC50 significantly lower than those of the free IRI group and the free RA+IRI group (both P<0.01). Combination index analysis demonstrated that both the free RA+IRI group and the RA-IRI@Lip group exhibited synergistic effects (combination index <1), with stronger synergism observed in the RA-IRI@Lip group. Transwell assay results demonstrated that RA-IRI@Lip exerted the most significant inhibitory effect on the migration and invasion of ATC cells. Flow cytometry results showed that RA-IRI@Lip significantly decreased the proportions of aldehyde dehydrogenase-positive cells and CD133-positive cells (both P<0.01).
CONCLUSIONS: RA-IRI@Lip was successfully prepared, achieving synergistic effects of differentiation therapy and chemotherapy of RA and IRI, thereby effectively eliminating ATC cells and CSCs.
METHODS: RA-IRI@Lip was obtained through the co-encapsulation of RA and IRI within liposomes, using the thin-film hydration method. The particle size, Zeta potential, encapsulation efficiency, and in vitro release profiles of RA-IRI@Lip were characterized. Hemolysis assay was conducted to evaluate blood compatibility. Cellular uptake of FITC-labeled liposomes was assessed. The in vitro anti-ATC effects were evaluated by cell counting kit-8 (CCK‑8), calcein‑AM/PI staining, and Transwell assay. The synergistic effect of RA and IRI was analyzed using the combination index, while flow cytometry was performed to detect the proportions of aldehyde dehydrogenase-positive cells and CD133-positive cells.
RESULTS: The prepared RA-IRI@Lip had an average particle size of (210.3±5.2) nm, a polydispersity index less than 0.3, and Zeta potential of －(13.7±2.3) mV. The encapsulation efficiencies of RA and IRI were (88.1±2.9)% and (86.8±1.6)%, respectively. In vitro release studies showed that RA-IRI@Lip significantly delayed the release of both RA and IRI, with 48-h cumulative release rates of (66.2±3.6)% and (77.7±4.1)%, respectively. Hemolysis assays demonstrated that all tested concentrations of RA-IRI@Lip exhibited hemolysis rates below 3%, indicating good hemocompatibility. Liposomes can be efficiently taken up by ATC cells after FITC labeling. CCK-8 and calcein-AM/PI staining demonstrated that RA-IRI@Lip significantly inhibited the viability of ATC cells and promoted cell death, with an IC50 significantly lower than those of the free IRI group and the free RA+IRI group (both P<0.01). Combination index analysis demonstrated that both the free RA+IRI group and the RA-IRI@Lip group exhibited synergistic effects (combination index <1), with stronger synergism observed in the RA-IRI@Lip group. Transwell assay results demonstrated that RA-IRI@Lip exerted the most significant inhibitory effect on the migration and invasion of ATC cells. Flow cytometry results showed that RA-IRI@Lip significantly decreased the proportions of aldehyde dehydrogenase-positive cells and CD133-positive cells (both P<0.01).
CONCLUSIONS: RA-IRI@Lip was successfully prepared, achieving synergistic effects of differentiation therapy and chemotherapy of RA and IRI, thereby effectively eliminating ATC cells and CSCs.