Design and tuning of ionic liquid–based HNO donor through intramolecular hydrogen bond for efficient inhibition of tumor growth

Abstract

Developing ionic liquid (IL) drugs broaden new horizons in pharmaceuticals. The tunable nature endows ILs with capacity to delivery active ingredients. However, the tunability is limited to screen ionic components, and none realizes the kinetic tuning of drug release, which is a key challenge in the design of IL drugs. Here, a series of ILs are developed using biocompatible ionic components, which realizes absorption of gaseous NO to yield IL-NONOates. These IL-NONOates serve as HNO donors to release active ingredient. The release kinetics can be tuned through configuring the geometric construction of ILs (release half-lives, 4.2 to 1061 min). Mechanism research indicates that the tunability depends on the strength of intramolecular hydrogen bond. Furthermore, the IL-based HNO donors exert pharmacological potential to inhibit tumor progression by regulating intratumoral redox state. Coupled with biosafety, these IL-based HNO donors with facile preparation and tunable functionalization can be promising candidates for pharmaceutical application.

Recent Advances in Ionic Liquids in Biomedicine

“…By tuning the structure of the IL, researchers were able to control release based on NO uptake into the IL-drug system. [89] More recently, ILs have been applied as transport enhancers in drug delivery applications, [90] where their interactions with the barrier tissues have enabled the delivery of large molecules through otherwise formidable barriers. Banerjee and coworkers [91] delivered insulin orally using a choline geranate based ionic liquid, which maintains the secondary structure and activity of the insulin.…”

“…By tuning the structure of the IL, researchers were able to control release based on NO uptake into the IL‐drug system. [ 89 ]…”

Evaluation of Ionic Liquids and Ionic Liquids Active Pharmaceutical Ingredients Inhibition in Elastase Enzyme Activity

“…Ionic liquids (ILs) are defined as organic salts formed by cations and anions with a melting point below 100 °C and they present interestingly physical properties such as extremely low vapor pressure, wide liquid temperature range, no inflammability, and high thermal and chemical stability [ 10 ].…”

Ecotoxicity and Hemolytic Activity of Fluorinated Ionic Liquids

“…The task-specific design of materials and the improvement of industrial processes through sustainable and greener ionic liquids (ILs) have emerged in the last decades in many fields of interest, such as catalysis [1][2][3], energy and electrochemistry [4], lubricants [5], the design of new materials for gas absorption [6], separation and extraction processes [7][8][9], the design of stimuli-responsive materials and sensors [10,11], and biomedical and pharmaceutical applications [12][13][14][15][16][17]. The application of ILs in such broad range of fields are supported by their great tuneability, since their final properties are dependent on the cation-anion selected pair.…”

“…The use of ILs in the pharmaceutical field have covered topics such as the screening for antifungal, antiviral, antioxidant and anticancer properties (such as the capacity to inhibit tumor progression), the design of new pharmaceutics and drug delivery systems, as well as the improvement of several analytical techniques and drug synthesis processes [12][13][14][15][16][17]. Furthermore, the urgent need to evaluate the antibacterial properties of ILs has also been noticed, in order to screen for new substances with potential pharmacological value that may represent a better alternative to traditional treatment and an advantage regarding the constant increment of antimicrobial resistances that hampers the treatment of several infections.…”