Plant-derived natural products are essential and prominent contributors to drug discovery, especially as anticancer agents. Medicinal plants used in alternative therapy are often obscured by poor definitions of the underlying mechanisms behind their bioactivity. In this study, we investigated the cytotoxic and mechanistic effects of an enriched bioactive fraction derived from Mondia whitei. Bioactivity-guided fractionation was performed using C18 solid-phase extraction. The cytotoxic effects were evaluated using the MTT assay, while cellular morphology and mechanistic pathways were examined through microscopy, acridine orange staining, cathepsin-based assay, and immunoblotting of apoptosis- and autophagy-related proteins. Chemical profiling of the fraction was conducted using GC–MS analysis. The enriched fraction exhibited enhanced cytotoxicity at low microgram concentrations. Morphological assessment revealed prominent cytoplasmic vacuolation, while acridine orange staining indicated the accumulation of acidic vesicles. Cathepsin-based assays and immunoblot analysis of LC3-I/II confirmed lysosomal involvement and autophagy perturbation, whereas increased p62 levels suggested disruption of the autophagy–lysosome perturbation. In parallel, activation of intrinsic apoptosis was evidenced by the increased expression of caspase-9 and caspase-3. GC–MS profiling tentatively identified lupeol and cis-vaccenic acid as the major constituents of the fraction. The results from these studies demonstrate that the enriched fraction of Mondia whitei induced vacuolation-associated cytotoxicity through autophagy–lysosome perturbation and caspase-dependent apoptosis, providing mechanistic insight into its anticancer potential.
Saheed O Anifowose, Mobarak S. Al Mosallam, E. Bahattab et al.· Biomolecules· 0 citations
RNA vaccines have emerged as an attractive platform for treating infectious diseases, cancer immunotherapy, and personalized medicine; however, their clinical success depends on multiple factors, including efficient, stable, and scalable delivery systems. Because RNA molecules are highly sensitive to factors such as enzymatic degradation, oxidation, poor cellular uptake, and limited endosomal escape, nanocarrier platforms play essential roles in protecting RNA cargo and enabling effective intracellular delivery. The biological performance of RNA nanocarriers depends on efficient cellular uptake, endosomal escape, intracellular RNA delivery, biodistribution, and immune modulation. Comparative assessment emphasizes that lipid nanoparticles remain the most clinically mature approach, while nanostructured lipid carriers, polymeric systems, and exosome-based nanocarriers provide multiple benefits for stability, targeted delivery, biocompatibility, and/or controlled release. Translational challenges involving GMP manufacturing, batch reproducibility, regulatory expectations, and scale-up are considered critical for effective nano-based RNA vaccine delivery and are elaborated in this review. Emerging advances such as pKa-tuned ionizable lipids, ligand-targeted systems, stimuli-responsive nanocarriers, circular and self-amplifying RNA platforms, artificial intelligence-guided formulation design, and needle-free delivery technologies may further expand the safety, accessibility, and therapeutic potential of RNA vaccines. In this review, we highlight next-generation nanocarrier systems for RNA vaccines, with an emphasis on novel nanocarrier RNA vaccine delivery systems. Additionally, we evaluate stability engineering approaches that currently limit global vaccine distribution and the future of the nanocarrier platforms for RNA vaccines.
Mohannad M. Fallatah, Samiyah Al-Khaldi, Dimah K. Alrabiah et al.· Pharmaceutics· 0 citations
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