Synthetic lethality is a molecular-targeted therapy for selective killing of cancer cells. We exploited a lethal interaction between superoxide dismutase 1 inhibition and Bloom syndrome gene product (BLM) defect for the treatment of colorectal cancer (CRC) cells (HCT 116) with a customized lung cancer screen-1-loaded nanocarrier (LCS-1-NC). The drug LCS-1 has poor aqueous solubility. To overcome its limitations, a customized NC, composed of a magnetite core coated with three polymeric shells, namely, aminocellulose (AC), branched poly(amidoamine), and paraben-PEG, was developed for encapsulating LCS-1. Encapsulation efficiency and drug loading were found to be 74% and 8.2%, respectively. LCS-1-NC exhibited sustained release, with ∼85% of drug release in 24 h. Blank NC (0.5 mg/mL) exhibited cytocompatibility toward normal cells, mainly due to the AC layer. LCS-1-NC demonstrated high killing selectivity (104 times) toward BLM-deficient HCT 116 cells over BLM-proficient HCT 116 cells. Due to enhanced efficacy of the drug using NC, the sensitivity difference for BLM-deficient cells increased to 1.7 times in comparison to that with free LCS-1. LCS-1-NC induced persistent DNA damage and apoptosis, which demonstrates that LCS-1-NC effectively and preferentially killed BLM-deficient CRC cells. This is the first report on the development of a potential drug carrier to improve the therapeutic efficacy of LCS-1 for specific killing of CRC cells having BLM defects.

Tuneable selectivity in cross-Glaser products is achieved by tweaking the catalyst-backbone. The interaction responsible for this is unravelled.

In the past few decades, click chemistry (CuAAC reaction) has seen tremendous development both in terms of catalyst designing and method development because 1,2,3triazoles products have shown enormous applications in various fields. The sought after azide-alkyne cycloaddition reaction catalyzed by smaller-sized (~7 nm) Cu(I/II) oxide nanoparticles (Cu I/II O NPs) supported by thiol-functionalized cellulose provided triazole products in excellent yields (90-98%) with remarkable 1,4-regioselectivity, including the 10 g scale synthesis of a rufinamide drug intermediate. The possible reasons for this exceptional activity are the higher ratio of Cu (I), along with the smaller-sized and homogeneously dispersed colloidal nature of Cu I/II O NPs. Most importantly, the reaction underwent industrially friendly greener conditions such as aqueous medium, room temperature, and no additives, etc., suggesting promising for practical applications. The as-prepared catalyst was recycled and reused up to 5 cycles by simply filtering the precipitate 1,2,3-triazoles products without losing significant activity.

To daze conventional pesticide release limitations, nanotechnology-mediated pesticide delivery using natural polymers has been actively investigated. However, the lack of information on what are the beneficial/non-beneficial aspects of using hybrid- and organic-nanoparticles (NP) and among the polysaccharides which are better suited concerning pesticide loading efficiency (PLE wt%), entrapment efficiency, and sustained pesticide release (SPR %) has prompted us to investigate this study. In this report, we systematically investigated a series of polysaccharides such as starch (S), cellulose (C), aminocellulose (AC), and sodium carboxymethylcellulose (NaCMC) coated on magnetite NP (MNP, Fe3O4) and complete organic nanocarrier systems (starch and cellulose) that have no MNP part were compared for the PLE wt% and SPR % efficiencies for chlorpyrifos (ChP) insecticide. Overall, all nanocarriers (NCs) have shown good to excellent PLE wt% due to the smaller-sized NP obtained through optimal conditions. However, among the hybrid polysaccharides studied, starch MNP has shown a maximum PLE of 111 wt% in comparison with other polysaccharides (80–94 wt%) coated hybrid-NCs as well as with organic-NCs (81–87 wt%). The use of inorganic support does improve the PLE wt% markedly for starch but not for cellulose derivatives. Similarly, the SPR results of S-NP showed a remarkably better sustained release profile for ChP of 88% in 14 d. In contrast, other unfunctionalized and functionalized celluloses exhibited poor release profiles of 60%–20% for the same period. This study may help the researchers choose the right system for designing and achieving enhanced pesticide efficiency.

The excess nitric oxide (NO) produced in the body in response to bacterial/proinflammatory stimuli is responsible for several pathological conditions. The current approaches that target the production of excess NO, either through the inhibition of nitric oxide synthase enzyme or its downstream mediators have been clinically unsuccessful. With an aim to regulate the excess NO, we developed urea‐functionalized push‐pull chromophores containing 1,1,4,4‐tetracyanobuta‐1,3‐dienes (TCBD) or expanded TCBD (eTCBD) as NO scavengers. The NMR mechanistic studies revealed that upon NO binding, these molecules are converted to uncommon stable NONOates. The unique emissive property of Urea‐eTCBD enables its application in vitro, as aNO‐sensor. Furthermore, the cytocompatible Urea‐eTCBD, rapidly inactivated the NO released from LPS‐activated cells. The therapeutic efficacy of the molecule in modulating NO‐mediated pathological condition was confirmed using a carrageenan‐induced inflammatory paw model and a corneal injury model. While the results confirm the advantages of scavenging the excess NO to address a multitude of NO‐mediated diseases, the promising sensing and bioactivity of Urea‐eTCBD can motivate further exploration of such molecules in allied areas of research.