A calix[4]arene-based ternary supramolecular nanoassembly with improved fluoroquinolone photostability and enhanced NO photorelease

Abstract

A calix[4]arene-based micellar nanoscaffold allows the co-encapsulation of a photolabile fluoroquinolone drug and a poorly photoreactive NO photodonor, simultaneously overcoming the main limitations of the free individual guests such as photolability and low photoreactivity.

Co-Loading of Temozolomide and Curcumin into a Calix[4]arene-Based Nanocontainer for Potential Combined Chemotherapy: Binding Features, Enhanced Drug Solubility and Stability in Aqueous Medium

“…p-Sulfonato-calixarenes are promising candidates for biomedical applications due to their high water-solubility, low toxicity and immunogenicity, and biocompatibility [28,29]. In a monomeric or nanoassembled form, they have been proposed as efficient carriers for a variety of drugs [28][29][30][31]. Recently, it has been reported that the inclusion of TMZ into the cavity of a monomeric p-sulfonato-calix [4]arene-OH (SC4OH, Figure 2a) protected the drug from the rapid hydrolysis and enhanced its efficacy against glioblastoma in in vitro and in vivo experiments [17].…”

Host–Guest-Interaction Enhanced Nitric Oxide Photo-Generation within a Pillar[5]arene Cavity for Antibacterial Gas Therapy

“…The increased nitro-aromatic twist angle from 12.3 to −21.8° suggests that the confined cavity of H may suppress the molecular motion of the guest molecule. However, the change of the nitro-aromatic torsion angle is much smaller than those in the papers, in which NO photoreleased from PhNO 2 derivatives is mainly attributed to the formation of almost 90° nitro-aromatic torsion angle. − Therefore, the subtle conformation change from the free G to the encapsulated G is not that significant to provide the remarkably enhanced photoactivity of G . Hence, to gain deeper insight into the structure–photoactivity relationship of encapsulated G in HG , excited-state calculations were then performed.…”

“…All reagents were commercially available and used as supplied without further purification. Compounds H and G were prepared according to the published procedures. The deionized water used was purified using a Millipore water purification system with a minimum resistivity of 18.0 MΩ·cm.…”

“…Previously, covalent functionalization 33−36 of PhNO 2 deriva-Scheme 1. Schematic Illustration of Enhanced NO Photo-Generation of Encapsulated G Triggered by the Spatial Confinement of Pillar [5]arene Cavity and the Broad-Spectrum Antibacterial, Biofilm Inhibition, and Dispersal Activities of this Light-Responsive NO-Generation Host−Guest (HG) System tives or loading them in micelles 38,39 or hydrogels 40 can avoid the utilization of detrimental UV light, but the NO-generation yield is still low; the formation of inclusion complexes of PhNO 2 derivatives and β-cyclodextrin 41 results in the generation of NO but with low photolysis quantum yield. Thus, it is still challenging to realize the high photoactivity of PhNO 2 derivatives and NO-generation yield upon visible light irradiation for antibacterial applications.…”

“…Nitric oxide (NO) used in antibacterial gas therapy is an attractive bactericidal agent, featuring the ability to kill bacteria, disperse biofilms, and promote bacteria-infected wound healing, while more importantly, avoiding resistance. − Nitrobenzene (PhNO 2 ) derivatives are a type of NO donor and can achieve precise spatiotemporal NO delivery under ultraviolet (UV) light. − However, the relatively poor photoactivity, utilization of cytotoxic UV light, insufficient NO generation, and significant cytotoxicity toward mammalian cells have limited their application in antibacterial treatments. Previously, covalent functionalization − of PhNO 2 derivatives or loading them in micelles , or hydrogels can avoid the utilization of detrimental UV light, but the NO-generation yield is still low; the formation of inclusion complexes of PhNO 2 derivatives and β-cyclodextrin results in the generation of NO but with low photolysis quantum yield. Thus, it is still challenging to realize the high photoactivity of PhNO 2 derivatives and NO-generation yield upon visible light irradiation for antibacterial applications.…”