SiO2–alginate–melittin nano-conjugates suppress the proliferation of ovarian cancer cells: a controlled release approach leveraging alginate lyase

Abstract

Background Ovarian cancer treatment is challenged by resistance and off-target effects. Melittin shows promise against cancer but is limited by its instability and harmful cellular interactions. Our study introduces SiO2–alginate–melittin nano-conjugates (SAMNs), incorporating alginate lyase to enhance melittin's release and mitigate alginate drawbacks. Methods We combined melittin with alginate and mesoporous silica, using alginate lyase to control melittin release. Effects on SKOV3 ovarian cancer cells were evaluated via viability, invasion, migration assays, ROS levels, apoptosis-related proteins, and mitochondrial function tests. Results SAMNs extended melittin’s cell control, reducing proliferation, invasion, and migration compared to free melittin. Alginate lyase facilitated controlled melittin release, decreasing off-target cytotoxicity. The only melittin group showed severe mitochondrial impairment, while the SAMNs and lyase groups had moderated impacts, indicating a dose-dependent effect on mitochondrial health and cell uptake. Conclusions SAMNs, especially with alginate lyase, offer an effective strategy for ovarian cancer treatment, optimizing melittin delivery while minimizing adverse effects of alginate. This approach enhances the therapeutic potential of melittin in combating ovarian cancer.

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“…In addition, a dose-dependent decrease in the mitochondrial membrane potential was observed. It is to be noted that the concentration of AL used in the current study is far below that reported by Si et al48…”

“…In line with this finding, it was reported that the addition of alginate lyase to melittin-loaded nanoparticles (without surface immobilization) showed concentration-dependent improvement in the cellular uptake studied on ovarian cancer cells. 48…”

“…two-way ANOVA with Tukey's post hoc test, p < 0.05) is then cell and concentration dependent. Si et al48 recently combined mesoporous silica with alginate and melittin in presence of alginate lyase to control melittin release. The effect on ovarian cancer cells (SKOV3) was evaluated in terms of viability, invasion, migration assays, ROS levels, apoptosis-related proteins, and mitochondrial function tests.…”