RESUMO
While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated by utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF which was conjugated to RST, forming core shell nanohybrids into which HK was physically loaded, followed by cross linking using genipin. The crosslinked HK-loaded PMT-ALG/LF-RST nanohybrids exhibited a fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an eight-fold decrease in the IC50 compared to the free drug combination, in addition to showing an enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for an effective breast tumor suppression.
RESUMO
BACKGROUND: At present, the prevalence of pregestational diabetes is 2.2% with an overall prevalence of hyperglycaemia in pregnancy of about 16.2%. Fetuses of diabetic mothers are at risk of functional cardiac abnormalities without structural cardiac anomalies especially in the third trimester. The main aim of this study was to assess the association of diabetes with different fetal echocardiographic parameters. METHODS: A case control study comprising a total of 120 pregnant women (60 cases and 60 controls). The cases group included fetuses of mothers known to have pre-gestational type 2 diabetes (DM group) while the control group included fetuses of euglycaemic healthy pregnant women. They were examined twice at 23-24 weeks' gestation (visit 1) and followed up at 27-28 weeks' gestation (visit 2). The Modified Myocardial Performance Index (Mod MPI) was obtained in all fetuses. Also, M-mode echocardiography was used to measure the interventricular septum thickness at diastole in a transverse four chamber view. RESULTS: There was a significant increase in Iso-volumetric contraction time (ICT) (45.4 ms ± 8.9), Iso-volumetric relaxation time (IRT) (54.7 ms ± 11.22), Interventricular septal thickness (IVST) (4.08 mm ± 0.8), aortic acceleration time (AAT) (54.16 ms ± 12.77) and MPI (0.64 ± 0.09) in the diabetic group compared to the normal control group ICT (38.5 ms ± 9.59), IRT (46.13 ms ± 10.29), IVST (3.17 mm ± 0.6), AAT (49.73 ms ± 10.68) and MPI (0.5 ± 0.1) (all P values were < 0.001). When comparing parameters assessed at both visits among diabetic patients, there was a significant increase in IVST in the second visit (4.74 ± 0.78 mm) compared to the first visit (4.08 ± 0.8 mm) (P value < 0.05). The incidence of hypertrophic cardiomyopathy (HCM) was significantly higher in diabetic patients than in the control group. This is was observed in both first and second visit (33.4% and 56.7%) (P value < 0.001). CONCLUSIONS: Fetuses of diabetic pregnant females show a significant increase in MPI, decrease in E\A ratio and HCM. These alterations in cardiac functions and structure were found to be continuous throughout the period of time between the two visits.