Nano-silymarin combined with methylene blue photodynamic therapy versus monotherapies of head and neck squamous cell carcinoma: in-vitro study.

Authors

Delband Hefzi, Maryam Koopaie, Neda Hakimiha, Shima Younespour

Published in

BMC cancer. Jun 29, 2026. Epub Jun 29, 2026.

Abstract

Head and neck squamous cell carcinoma (HNSCC) presents significant therapeutic challenges due to its aggressiveness and the morbidity of conventional treatments. Photodynamic therapy (PDT) offers a localized approach, but its efficacy can be limited. This study investigated the potential of nano-silymarin, a bioactive flavonolignan complex with known anticancer properties, in combination with methylene blue-mediated PDT (MB-PDT) in HNSCC cells.
The cytotoxic, apoptotic, and anti-migratory effects of various treatments were assessed in HN5 cells. Groups included controls, individual agents (nano-silymarin, MB, laser), dual therapies, and the triple combination (nano-silymarin + MB + laser). Cell viability was measured using the MTT assay, apoptosis by flow cytometry, and migration by the scratch assay. Results were analyzed using one-way ANOVA with Tukey's post hoc test. Synergy was quantified using the Bliss independence, Loewe additivity, and zero interaction potency models.
The triple combination (nano-silymarin + MB-PDT) demonstrated the most potent effect, synergistically reducing cell viability to 40.63% (compared with 69.65% for nano-silymarin and 77.32% for MB-PDT). It induced the highest level of total apoptosis (42.93%) and nearly completely inhibited cell migration (97.2% wound openness at 72 h). This anti-migratory effect was significantly greater than the sum of the effects of the individual monotherapies, indicating a synergistic blockade of cellular invasion. Synergy analysis confirmed a strong synergistic interaction, with a Combination index of 0.682.
Nano-silymarin significantly potentiates the anticancer efficacy of MB-PDT against HNSCC cells through strong synergistic interactions, thereby enhancing cytotoxicity, apoptosis, and migration inhibition. These findings support further development of nano-silymarin in combinatorial PDT regimens for HNSCC.

PMID:
42374269
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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