RESUMEN
Background: Breast cancer is the leading cause of frequent malignancy and morbidity among women across the globe, with an increment of 0.5% incidences every year. The deleterious effects of traditional treatment on off-target surrounding cells make it difficult to win the battle against breast cancer. Hence, an advancement in the therapeutic approach is crucial. Nanotechnology is one of the emerging methods for precise, targeted, and efficient drug delivery in cells. The previous study has demonstrated the cytotoxic effect of Ipomoea turpethum extract on breast cancer cells delivered via NIPAAM-VP-AA nanoparticles (NVA-IT). Manipulating the tumor microenvironment (TME) to inhibit cancer progression, invasion, and metastasis seems to be very insightful for researchers these days. With the help of secretome analysis of breast cancer cells after treatment with NVA-IT, we have tried to find out the possible TME manipulation achieved to favor a better prognosis of the disease. Method: MCF-7 and MDA MB-231 cells were treated with the IC50 value of NVA-IT, and the medium was separated from the cells after 24 h of the treatment. Nano LCMS/MS analysis was performed to identify the secretory proteins in the media. Further bioinformatics tools like GENT2, GSCA, GeneCodis 4, and STRING were used to identify the key proteins and their interactions. Result: From the nano LCMS/MS analysis, 70 differentially expressed secretory proteins in MCF-7 and 191 in MDA MB-231 were identified in the cell's media. Fifteen key target proteins were filtered using bioinformatics analysis, and the interaction of proteins involved in vesicular trafficking, cell cycle checkpoints, and oxidative stress-related proteins was prominent. Conclusion: This study concluded that I. turpethum extract-loaded NIPAAM-VP-AA nanoparticles alter the secretory proteins constituting the TME to cease cancer cell growth and metastasis.
RESUMEN
Introduction: Artemisia absinthium (wormwood) exhibits anticancer properties by inhibiting proliferation and causing cell death in breast cancer. Targeted drug delivery of A. absinthium nanoformulation using N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid-based polymeric nanoparticles (NVA-AA NPs) was ensured by utilizing features of the tumor microenvironment, although their mechanism of action involved in cytotoxicity remains unknown. Methods: The present study employed nano LC-MS/MS to identify differences in secretory protein expression associated with the treatment of breast cancer cell lines (MCF-7; MDA-MB-231) by NVA-AA NPs for the determination of affected pathways and easily accessible therapeutic targets. Different bioinformatics tools were used to identify signature differentially expressed proteins (DEPs) using survival analysis by GENT2 and correlation analysis between their mRNA expressions and sensitivity toward small-molecule drugs as well as immune cell infiltration by GSCA. Results: Analysis by GENT2 revealed 22 signature DEPs with the most significant change in their expression regulation, namely, gelsolin, alpha-fetoprotein, complement component C3, C7, histone H2B type 1-K, histone H2A.Z, H2AX, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1-like, cytochrome c somatic, GTP-binding nuclear protein Ran, tubulin beta chain, tubulin alpha-1B chain, tubulin alpha-1C chain, phosphoglycerate mutase 1, kininogen 1, carboxypeptidase N catalytic chain, fibulin-1, peroxiredoxins 4, lactate dehydrogenase C, SPARC, and SPARC-like protein 1. Correlation analysis between their mRNA expressions versus immune cell infiltrates showed a positive correlation with antitumor immune response elicited by these NPs as well as a correlation with drug response shown by the GDSC and CTRP drugs in different cancer cells. Discussion: Our results suggest that NVA-AA NPs were able to invade the tumor microenvironment; transformed the communication network between the cancer cells; affected potential drivers of microtubular integrity, nucleosome assembly, and cell cycle; and eventually caused cell death.
RESUMEN
Background: This study was designed to quantify the composition of the ethanolic extract of Artemisia absinthium through gas chromatography-mass spectrometry analysis and ensure in vivo safety of A. absinthium extract-loaded polymeric nanoparticles (ANPs) before considering their application as a drug carrier via the oral route. Methods: We synthesized N-isopropylacrylamide, N-vinyl pyrrolidone, and acrylic acid crosslinked polymeric NPs by free-radical polymerization reaction and characterized them by Fourier-transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering spectroscopy. Different concentrations of extract (50 mg/kg, 300 mg/kg, and 2,000 mg/kg body weight) were encapsulated into the hydrophobic core of polymeric micelles for the assessment of acute oral toxicity and their LD50 cut-off value as per the test procedure of OECD guideline 423. Orally administered female Wistar rats were observed for general appearance, behavioral changes, and mortality for the first 30 min, 4 h, 24 h, and then, daily once for 14 days. Result: ANPs at the dose of 300 mg/kg body weight were used as an initial dose, and rats showed few short-lived signs of toxicity, with few histological alterations in the kidney and intestine. Based on these observations, the next set of rats were treated at a lower dose of 50 mg/kg and a higher dose of 2,000 mg/kg ANPs. Rats administered with 50 mg/kg ANPs remained normal throughout the study with insignificant histological disintegration; however, rats treated at 2,000 mg/kg ANPs showed some signs of toxicity followed by mortality among all three rats within 24-36 h, affecting the intestine, liver, and kidney. There were no significant differences in hematological and biochemical parameters among rats treated at 50 mg/kg and 300 mg/kg ANPs. Conclusion: We conclude that the LD50 cut-off value of these ANPs will be 500 mg/kg extract loaded in polymeric NPs.
RESUMEN
Introduction: The amalgamation of novel drug delivery techniques and potential drugs is considered the most promising tool for the treatment of diseases. In our study, we have employed N-isopropyl acrylamide, N-vinyl pyrrolidone, and acrylic acid (NIPAAM-VP-AA) copolymeric nanoparticles for delivering Ipomoea turpethum root extract. I. turpethum is a perennial herb (Convolvulaceae family) and has been used as medicine for ages. The present study was conducted to evaluate the safety of I. turpethum root extract-loaded NIPAAM-VP-AA polymeric nanoparticles (NVA-IT) in Wistar rats. Methods: An acute oral toxicity study was conducted in accordance with OECD guidelines 423 for the testing of chemicals. Different doses of NVA-IT i.e., 5 mg/kg, 50 mg/kg, 300 mg/kg, and 2000 mg/kg were administered to female Wistar rats in a stepwise manner using oral gavage. The toxicity signs were thoroughly observed for the next 14 days. At the end of the study, the blood and vital organs were harvested for hematological, biochemical, and histopathological studies. Result: No mortality or pathological anomalies were observed even at the highest dose which exemplifies that the lethal dose would be more than 2000 mg/kg body weight (GSH category 5). Behavioral changes, biochemical parameters, and histopathology of vital organs were normal after NVA-IT administration. Conclusion: This study demonstrated that NVA-IT nanoparticles are non-toxic and can be considered for therapeutic use in different diseases, such as inflammation, CNS diseases, Cancer, etc.
RESUMEN
BACKGROUND: Polycystic ovarian syndrome has emerged as a cardiometabolic disorder and aim of this study was to evaluate various surrogate indices and their diagnostic potential to determine the most convenient and cost-effective marker of IR, CVD, and MetS in these women. MATERIALS AND METHODS: Ninety-five PCOS women and 45 age matched healthy women were enrolled. Measures included anthropometric and biochemical parameters, BMI, WHR, WHtR, BAI, VAI, LAP, HOMA-IR, and lipid profile. RESULTS: LAP has highest AUC value 0.781 with cut-off value = 39.73 (sensitivity = 75% and specificity = 79.5%) for predicting IR and AUC value 0.83 with cut-off value = 35.63 (sensitivity = 94.4% and specificity = 77.3%) for predicting MetS in women with PCOS. LAP had statistically strong positive correlation with WC, BMI, WHR, fasting glucose, fasting insulin, HOMA-IR, TC, TG, and SBP. CONCLUSIONS: LAP is a powerful and reliable marker for assessment of IR, CVD, and MetS risk in young Indian women with PCOS.