👤 Nur Balqis Zamri

Autophagy, a critical homeostatic process, is increasingly implicated in cancer progression and therapy resistance. SAR405 is a potent inhibitor of the autophagy related PIK3C3/VPS34 complex, offering potential as an anticancer agent. This study reports the synthesis, characterization, and biological evaluation of SAR405-loaded chitosan nanoparticles (CNP-SAR405) designed to improve therapeutic delivery and efficacy in A549 human lung carcinoma cells. CNPs were prepared via ionic gelation using chitosan and sodium tripolyphosphate (TPP), yielding stable monodisperse nanoparticles ~ 77.4 nm, PDI ~ 0.2). Upon SAR405 encapsulation, nanoparticle size increased to ~ 110 nm while maintaining uniform distribution. Encapsulation efficiency reached 80% at 200 nM SAR405, confirmed by UV-Vis spectroscopy. Morphological analyses using FESEM and TEM verified spherical nanoparticle structures, while FTIR confirmed successful SAR405 incorporation. FITC-labelling enabled real-time tracking of intracellular uptake, revealing detectable internalization as early as 12 h post-treatment, with fluorescence intensity peaking at 72 h. In vitro cytotoxicity assays demonstrated enhanced anticancer efficacy of CNP-SAR405 compared to free SAR405, CNP-SAR405 achieved similar cytotoxic effects at 69 nM compared to 100 nM for free SAR405 in A549 cells. Furthermore, co-treatment with the autophagy inducer Torin-2 validated that CNP-SAR405 more effectively inhibited autophagosome formation than SAR405 alone, particularly at the 24-h mark. These findings underscore the potential of chitosan nanoparticle-mediated delivery to increase SAR405 bioavailability and anticancer potency while achieving comparable cytotoxic at a lower dose than free SAR405. The CNP-SAR405 formulation represents a promising nanotechnology-driven approach to targeted lung cancer therapy. All experiments were performed in triplicate biological replicates with technical triplicates, and data were analysed using one-way ANOVA followed by Tukey's multiple comparison post-hoc test (p < 0.05 considered significant). Show less

Obesity is a pressing public health issue in Malaysia, involving not only excess weight but also complex metabolic and physiological changes. Addressing these complexities requires comprehensive strategies, including understanding the population-level differences in obesity susceptibility. This review aims to compile the genetic variants studied among Malaysians and emphasize their implications for obesity risk. Relevant articles published up to March 2024 were extracted from the Scopus, PubMed, and ScienceDirect databases. The review process was conducted in accordance with the PRISMA-ScR guidelines. From an initial pool of 579 articles, 35 of these were selected for the final review. The identified gene variants, including Overall, more intensive genetic research is needed, starting with population-based profiling of genetic data on obesity, including among children. Sociocultural contexts and environmental factors influence variations in genetic elements, highlighting the need for targeted interventions to mitigate the impacts of obesity in the population. Show less