Synergistic Effect of Lutein Combined With 5‐Fluorouracil‐Encapsulated Niosomes for Breast Cancer Treatment

Breast cancer remains the most prevalent cancer in women globally, with cases projected to exceed 3 million by 2040. Current treatments, including chemotherapy with 5‐fluorouracil (5FU), are often hindered by multidrug resistance (MDR) and significant toxicities. This study investigated the potential of lutein (Lut), a bioactive xanthophyll with pro‐oxidant activity that could enhance 5FU’s efficacy while reducing the dosage in MCF‐7 cells analyzed via CompuSyn software. The result revealed that the Lut:5FU combination at a ratio of 0.25:1 had a synergistic effect at Fraction affected (Fa) of 0.49 with a combination index (CI) value of 0.09, indicating synergistic effects (CI < 1), and the dose‐reduction index (DRI) of Lut and 5FU was 11.27‐ and 277.16‐fold, respectively. Moreover, Lut encapsulation in niosomes could protect Lut’s photodegradation, offer controlled release, and enhance cancer cell inhibition. In addition, the total cell death of Lut:5FU encapsulated in niosomes (Lut:5FU‐N) was investigated by apoptosis assay, which was the highest efficacy at 43.11 ± 3.29% compared to Lut encapsulated in niosomes (Lut‐N) and 5FU encapsulated in niosomes (5FU‐N) as a single treatment (32.27 ± 1.17 and 24.97 ± 1.96%, respectively). This study presented that Lut could improve the therapeutic efficacy of 5FU by combination and encapsulation in niosomes for breast cancer treatment, providing a promising strategy to enhance anticancer effects, address the limitations of conventional cytotoxic agents, and mitigate associated toxicities.