В обзоре приведены основные методы получения наночастиц благородных металлов, способы функционализации их поверхности; рассмотрена фармакокинетика и возможные механизмы химиотерапевтического действия наночастиц золота: индукция апоптоза, активация липопероксидации, ингибирование мембранного транспортера гликопротеина-P. Также описывается перспективный вариант противоопухолевой фармакотерапии — использование гликонаночастиц золота с поверхностью, модифицированной моносахаридными остатками, имеющими тропность к лектинам опухолевых клеток. Подобная тактика позволяет достичь их адресной (таргетной) доставки в трансформированную ткань с минимизацией риска системной токсичности.

INTRODUCTION: Use of metal nanoparticles is a promising trend in oncotherapy. AIM: To evaluate cytotoxicity of gold nanoparticles (GNPs) modified with fucose, lactose and galactose residues, on Caco-2 cells. MATERIALS AND METHODS: Cells were cultured to a monolayer with GHPs in concentrations of 10 g/ml600 g/ml for particles with fucose, 10 g/ml900 g/ml for particles with lactose and 10 g/ml550 g/ml for particles with galactose. As non-tumor cells, Caco-2 cells were used after differentiation into small-intestine enterocytes (incubation time 21 days). The cytotoxicity of GNPs was evaluated in MTT-test after incubation with cells for 2 hours, 8 hours and 24 hours. A comparison drug was fluorouracil in concentrations of 50 g/ml2000 g/ml. The half-maximal inhibitory concentration (IC50) was calculated in GraphPad Prism 8.4.3 program. RESULTS: IC50 for GNPs with fucose for tumor cells was 582 29 and 336 36 g/ml after incubation for 2 hours and 8 hours, respectively; for GNPs with lactose 769 50 and 515 45 g/ml, for GNPs with galactose 467 299 and 299 28 g/ml. For differentiated cells, IC50 for all types of GNPs was higher than for tumor cells after incubation for 2 and 8 hours: for particles with fucose 530 3 and 410 15 g/ml; for particles with lactose 831 7 and 639 14 g/ml; for particles with galactose 511 21 (p = 0.018) and 376 36 g/ml, respectively. After 24-hour incubation of Caco-2 cells with fucose, IC50 did not differ for tumor and differentiated varieties. For other GNPs, IC50 for tumor cells was higher than for differentiated cells. Fluorouracil showed cytotoxicity for tumor cells with IC50 2108 19 and 1764 193 g/ml after 2 hours and 8 hours of incubation, respectively. For differentiated cells, IC50 of fluorouracil was 1694 102 g/ml after 2-hour incubation and 1694 102 g/ml after 8-hour incubation. There were no differences between IC50 of fluorouracil for differentiated and tumor cells with equal incubation time. CONCLUSION: GNPs with fucose, lactose and galactose have a cytotoxic effect on human colon adenocarcinoma cells and in the activity are superior to fluorouracil.

Изучен возможный механизм противоопухолевой активности наночастиц золота (НЧЗ) с поверхностью, модифицированной остатками углеводов, тропных к мембранным лектинам опухолевых клеток, на клетках аденокарциномы ободочной кишки человека (Caco-2). Клетки Caco-2 инкубировали в течение 2 и 8 ч с растворами НЧЗ. НЧЗ снижали уровень SH-групп при 2-часовой инкубации с клетками в среднем в 20 раз (p < 0,05), при 8-часовой инкубации — в среднем в 10 раз (p < 0,05). Снижение трансмембранного потенциала митохондрий наблюдалось через 8 ч инкубации с НЧЗ с поверхностью, модифицированной фукозой и лактозой, в среднем до 58 % (p < 0,05). НЧЗ, модифицированные остатками фукозы, после 8-часовой инкубации повышали уровень малонового диальдегида (МДА) более чем в 1,5 раза (p < 0,05), а количество проапоптотического транскрипционного фактора p53 — более чем в 2,5 раза (p < 0,05). Таким образом, НЧЗ с поверхностью, модифицированной остатками фукозы, лактозы и галактозы, оказывают цитотоксический эффект на клетки Caco-2, реализуя свое действие за счет активации перекисного окисления липидов (Au-Fuc), а также, возможно, инициации одного из путей апоптоза через стимуляцию транскрипционного фактора p53 и снижение трансмембранного потенциала митохондрий.

Background: The combination of chronic obstructive pulmonary disease (COPD) and tuberculosis forms a specific clinical and pathogenetic phenotype. Studying the cytokine profile in comorbid pathology is necessary to understand the mechanisms of mutual aggravation of disease course. Aim: To assess the strength of association between serum levels of key cytokines and clinically significant manifestations of comorbid COPD and tuberculosis, with a primary focus on the presence of bacterial shedding. Methods: A single-center observational comparative cross-sectional study was conducted. From December 2024 to March 2026, clinical and laboratory parameters, serum cytokine levels, and the presence of Mycobacterium tuberculosis in sputum were evaluated in men aged 45 years and older followed up in pulmonology and phthisiology departments for COPD, pulmonary tuberculosis, or their combination, as well as in healthy volunteers in the control group. Serum levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Mycobacterium tuberculosis (MTB) isolation was assessed by sputum smear microscopy, fluorescent microscopy and/or sputum culture. Patients with a positive result were classified as MTB+, while those without confirmed bacterial shedding were classified as MTB-. Results: Data from 209 men were analyzed: 42 healthy volunteers (control group); 63 patients with COPD without active tuberculosis (COPD group); 51 patients with active pulmonary tuberculosis without comorbid COPD (TB group); and 53 patients with both COPD and active pulmonary tuberculosis (COPD + TB group). Median age across groups ranged from 64 to 69 years (p = 0.137). The groups differed significantly in smoking history, forced expiratory volume in 1 second (FEV1), oxygen saturation (SpO2), and markers of systemic inflammation. The comorbid group (COPD + TB) had the highest smoking history (median 31 pack-years), lowest FEV1 (41.3% of predicted), highest C-reactive protein (32.7 mg/L), and lowest SpO2 (90%) (all p 0.001). Levels of all five cytokines increased from the control group to the comorbid group (COPD + TB): median IL-6 from 6.3 to 51.7 pg/mL, IL-1β from 3.1 to 27.1 pg/mL, IL-8 from 18.4 to 66.0 pg/mL (all p 0.001). In bacterial shedders (MTB+, n = 59), cytokine levels were higher than in patients without bacterial shedding (MTB-, n = 45): IL-1β, 32.9 vs 13.2 pg/mL; IL-10, 29.1 vs 13.4 pg/mL; TNF-α, 30.0 vs 15.3 pg/mL (all p 0.001). The best discriminative ability for bacterial shedding was shown by IL-10 (AUC = 0.924) and TNF-α (AUC = 0.923). A multivariate logistic model including IL-1β, IL-6, TNF-α and the IL-6/IL-10 ratio demonstrated an in-sample AUC of 0.991 (95% confidence interval 0.979–1.000), and 0.974 (SD 0.009) after cross-validation. Conclusion: Serum cytokine levels are strongly associated with bacterial shedding. The cytokine profile may be considered as a research tool for stratifying the inflammatory phenotype in combined COPD and pulmonary tuberculosis.