Enhanced Cytotoxic Effects of Docetaxel-Loaded Solid Lipid Nanoparticles (SLN-DTX) on Gastric Adenocarcinoma In Vitro

多西他赛负载固体脂质纳米颗粒(SLN-DTX)对体外胃腺癌的细胞毒性作用增强

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Abstract

Gastric cancer is one of the leading causes of mortality worldwide. Despite recent advances in cancer therapy, there has been little change in cure and survival rates in patients suffering from gastric cancer. The use of conventional chemotherapeutic agents such as docetaxel is limited by some disadvantages such as alopecia and hematotoxicity. This study focused on the antitumor effects of solid lipid nanoparticles loaded with docetaxel (SLN-DTX) on gastric adenocarcinoma cells. SLN-DTX showed cytotoxicity against cancer cells (AGS), demonstrating an IC50 value lower than the concentration of free DTX after 24 h of treatment, evidencing the efficiency of nanoparticles. Morphological analysis revealed structural alterations, including cell rounding and reduced cytoplasmic projections posttreatment. SLN-DTX and DTX induced damage to microtubules, binding proteins, and core fragmentation, impairing cell adhesion and proliferation. They also showed changes in analyses involving cellular organelles (mitochondria and lysosomes) and cellular metabolism. SLN-BLANK did not show significant toxicity in the AGS tumor lineage in any assays, behaving similarly to the untreated control. Association of docetaxel with solid lipid nanoparticles (SLN-DTX) demonstrates significant efficiency in inducing cytotoxic effects in gastric adenocarcinoma cells, since this formulation exhibited potent antitumor activity. Treatment with nanostructured docetaxel caused morphological and metabolic changes in addition to altering the release of molecules relevant to tumor progression. These findings support the potential use of SLN-DTX as a promising drug delivery system, offering an innovative and effective approach for gastric cancer treatment while potentially reducing the side effects associated with conventional therapies.

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