Ulvan Microneedles Loaded with Photosensitizer 5-aminolevulinic Acid Inhibits Human Cervical Cancer HeLa Cells In vitro

BACKGROUND: Cervical cancer encompasses highly invasive and metastatic malignant tumors with poor prognoses. Recently, microneedles have gained significant attention as a novel, non-invasive drug delivery method, offering unique advantages in tumor treatment. OBJECTIVE: This study aims to develop an ulvan-based microneedle delivery system encapsulating the photosensitizer 5-aminolevulinic acid (5-ALA-UMNs) and to investigate its inhibitory effects on the growth of human cervical cancer Hela cells. METHODS: The 5-ALA-UMNs and UMNs (without photosensitizer) were fabricated using a two-step casting technique. The microneedles' morphology, puncture performance, and mechanical strength were assessed. Hela cells were treated in vitro with 5-ALA-UMNs, and the cellular uptake of the photosensitizer was observed using inverted fluorescence microscopy. Cell viability was determined by the CCK-8 assay to identify the optimal drug concentration. Additionally, the anti-tumor efficacy of 5-ALA-UMNs, induced via photodynamic therapy, was evaluated by Live-Dead staining and flow cytometry. RESULTS: The microneedles exhibited a uniform quadrangular pyramidal shape, orderly arrangement, intact needle tips, and robust mechanical strength. Inverted fluorescence microscopy confirmed the successful uptake of the photosensitizer by Hela cells, which enzymatically converted it to the fluorescent compound protoporphyrin IX. CCK-8 assays demonstrated that 5-ALA-UMNs displayed favorable cytocompatibility and safety. Liver-dead staining revealed Hela cell survival rates as follows: 99.55% in the control group, 99.37% in the control microneedle group, 99.41% in the 5-ALA-UMNs group without light exposure, and 57.35% in the 5-ALA-UMNs group with light exposure (all p < 0.05). Flow cytometry results corroborated the live-dead staining findings, confirming the cytotoxic effect of 5-ALA-UMNs on tumor cells. CONCLUSION: These results indicate that 5-ALA-UMNs hold promise as a tumor-targeting therapeutic.