Covalent organic frameworks (COFs) having periodicity in pores of nanoscale dimensions can be suitably designed for the organic building units bearing reactive functional groups at their surfaces. Thus, they are an attractive option as an anticancer agent to overcome the limitations of chemotherapy. Herein, we first report a new porous biodegradable nitrogen containing COF material, EDTFP-1 (ethylenedianiline-triformyl phloroglucinol), synthesized using 4,4'-ethylenedianiline and 2,4,6-triformylphloroglucinol via Schiff base condensation reaction. EDTFP-1 exhibited 3D-hexagonal porous structure with average pores of ca. 1.5 nm dimension. Here, we have explored the anticancer potentiality of EDTFP-1. Result demonstrated an enhanced cytotoxicity was observed against four cancer cells HCT 116, HepG2, A549, and MIA-Paca2 with significant lower IC on HCT116 cells. Additionally, EDTFP-1-induced cell death was associated with the characteristic apoptotic changes like cell membrane blebbing, nuclear DNA fragmentation, externalization of phosphatidylserine from the cell membrane followed by a loss of mitochondrial membrane potential as well as modulation of pro and antiapoptotic proteins. Further, the result depicted a direct correlation between the generations of ROS with mitochondrial-dependent apoptosis through the involvement of p53 phosphorylation upon EDTFP-1 induction, suggesting this COF material is a novel chemotherapeutic agent for cancer treatment.

Background: Diabetic nephropathy (DN), an end-stage renal disorder, has posed a menace to humankind globally, because of its complex nature and poorly understandable intricate mechanism. In recent times, functional foods as potential health benefits have been gaining attention of consumers and researchers alike. Rich in antioxidants, the peel and seed of pomegranate have previously demonstrated protection against oxidative-stress-related diseases, including cardiovascular disorders, diabetes, and cancer. Purpose: This study was designed to investigate the ameliorative role of pomegranate peel extract-stabilized gold nanoparticle (PPE-AuNP) on streptozotocin (STZ)-induced DN in an experimental murine model. Methods: Following the reduction methods, AuNP was prepared using the pomegranate peel ellagitannins and characterized by particle size, physical appearance, and morphological architecture. Modulatory potential of PPE-AuNP was examined through the plethora of biochemical and high throughput techniques, flow cytometry, immunoblotting, and immunofluorescence. Results: The animals treated with PPE-AuNP markedly reduced the fasting blood glucose, renal toxicity indices, and serum TC and TG in a hyperglycemic condition. As evident from an increased level of plasma insulin level, PPE-AuNP normalized the STZ-induced pancreatic β-cell dysfunction. The STZ-mediated suppression of endogenous antioxidant response was restored by the PPE-AuNP treatment, which reduced the generation of LPO as well as iROS. Furthermore, the hyperglycemia-mediated augmentation of protein glycation, followed by the NOX4/p-47 phox activation, diminished with the application of PPE-AuNP. The histological and immunohistochemical findings showed the protective efficacy of PPE-AuNP in reducing STZinduced glomerular sclerosis and renal fibrosis. In addition, it reduced proinflammatory burden through the modulation of the MAPK/NF-κB/STAT3/cytokine axis. Simultaneously, PI3K/ AKT-guided Nrf2 activation was evident upon the PPE-AuNP application, which enhanced the antioxidant response and maintained hyperglycemic homeostasis. Conclusion: The findings indicate that the use of PPE-AuNPs might act as an economic therapeutic remedy for alleviating DN.

Given that basal levels of reactive oxygen species (ROS) are higher in cancer cells, there is a growing school of thought that endorses pro-oxidants as potential chemotherapeutic agents. Intriguingly, cerium oxide (CeO 2 ) nanoparticles can manifest either anti-or pro-oxidant activity as a function of differential pH of various subcellular localizations. In an acidic pH environment, for example, in extracellular milieu of cancer cells, CeO 2 would function as a pro-oxidant. Based on this concept, the present study is designed to investigate the pro-oxidant activities of CeO 2 in human colorectal carcinoma cell line (HCT 116). For comparison, we have also studied the effect of ceria nanoparticles on human embryonic kidney (HEK 293) cells. Dose-dependent viability of cancerous as well as normal cells has been assessed by treating them independently with CeO 2 nanoparticles of different concentrations (5−100 μg/mL) in the culture media. The half maximal inhibitory concentration (IC 50 ) of nanoceria for HCT 116 is found to be 50.48 μg/mL while that for the HEK 293 cell line is 92.03 μg/mL. To understand the intricate molecular mechanisms of CeO 2 -induced cellular apoptosis, a series of experiments have been conducted. The apoptosis-inducing ability of nanoceria has been investigated by Annexin V-FITC staining, caspase 3/9 analysis, cytochrome c release, intracellular ROS analysis, and mitochondrial membrane potential analysis using flow cytometry. Experimental data suggest that CeO 2 treatment causes DNA fragmentation through enhanced generation of ROS, which ultimately leads to cellular apoptosis through the p53-dependent mitochondrial signaling pathway.

pH-Sensitive quercetin/Fe3O4 NPs loaded functionalized mesoporous SBA-15 fabricated for targeted drug delivery to colorectal carcinoma cells with high anti-carcinogenic efficacy.