Antioxidant and anticancer properties of citrus-mediated nanoformulations revealed by meta-analysis

This study aims to explore and analyse the potential antioxidant and anticancer potential of various citrus-mediated nanoformulations (CMNs), focusing on their effectiveness in scavenging free radicals and inducing cytotoxicity in cancer cells. This research employs a meta-analysis approach to assess data from multiple studies on CMNs. This study is the first meta-analysis to evaluate the antioxidant and anticancer properties of CMNs concurrently. This study offers a novel perspective by examining citrus species, plant parts utilised, nanoparticle types, particle sizes, and coating materials. The analysis employs the Population, Intervention, Comparison, and Outcome (PICO) framework and complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis utilizes Hedges' effect size and includes validation through fail-safe N. The IC₅₀ evaluation (µg/mL) revealed a significant effect of CMNs on antioxidant activity (d₊₊ = 3.49; P < 0.05). The IC50 value of 3.49 in the CMN indicates that a lower concentration is sufficient to inhibit 50% of the free radical activity, reflecting a stronger antioxidant potential than that of the control group. However, the overall antioxidant assay results (d₊₊ = 0.2; P = 0.309) and radical inhibition (%) for CMNs (d₊₊ = 0.1; P = 0.602) did not significantly differ. Subgroup analysis provided further insights, showing that both citrus peel and polyvinyl alcohol significantly reduced IC₅₀ values (d₊₊ >1; P < 0.05). In addition, radical inhibition significantly increased in CMNs derived from Citrus paradisi (d₊₊ = 3.05; P = 0.015), followed by those derived from Citrus limon (d₊₊ = 2.25; P < 0.01) and Citrus reticulata (d₊₊ = 1.03; P = 0.025). Various types of nanoformulations, such as Ag chitosan-NP (silver nanoparticle with chitosan), Ag-NP (silver nanoparticles), cerium dioxide nanoparticle (CeO₂-NPs), hydrogel-based nanocomposite (Hydrogel-NPCs), pectin-based nanoemulsion (Pectin-NPEs), titanium dioxide nanoparticle (TiO₂-NP), and whey-based nanoemulsion (Whey-NPEs), also significantly enhanced free radical scavenging activity (d₊₊ >1; P < 0.01). In terms of anticancer activity, CMN has a strong effect size (|d₊₊| >1; P < 0.05), with species such as Citrus macroptera and plant parts such as juice showing highly positive effects (d₊₊ = 2.25; P < 0.001). Additionally, nanoparticles with sizes between 101 and 500 nm exhibited significant effectiveness (d₊₊ = 2.26; P < 0.001). These findings indicate that citrus-derived compounds have potential as anticancer agents by actively enhancing the antioxidant capacity of healthy cells. The significant antiproliferative activity observed across multiple cancer cell lines, supported by robust statistical analyses, demonstrates the potential of CMNs as a natural therapeutic approach for cancer prevention and treatment.