NANOSTRUCTURED CALIX[4]ARENES FOR ANTIBACTERIAL PHOTOTHERAPY

In the search of innovative agents able to combat the antibiotic resistance phenomenon which is a serious threat for public health in the world, nitric oxide (NO) and singlet oxygen (1O2) radicals are very interesting "non-conventional" drugs. They elicit a significant broad spectrum toxicity against virus, bacteria, fungi, yeast, and protozoa by oxidation of cell components as proteins, lipids, and DNA. A growing interest there is for new compounds generating NO and 1O2 in a controlled fashion due to the high cytotoxicity, short half-life and diffusion in the cellular environment over short distances of these radicals. Light is a biofriendly stimulus that offers advantages in terms of precise spatiotemporal control and powerful trigger, it is does not affect physiological parameters such as temperature, pH, and ionic strength. Therefore, among the variety of NO and 1O2 generators, photochemical compounds are particularly appealing to confine the cytotoxic action in the area of interest sparing healthy cells. In this contribute, we exploited the calix[4]arene macrocycle to realize new nanoconstructs for photodisinfection and antibacterial phototherapy by using both a covalent and non-covalent approach. In the first case, multiple units of a NO photodonor have been clustered and spatially organized onto a polycationic calix[4]arene scaffold; in the second case multiple units of insoluble or scarcely water soluble NO and 1O2 photodonors have been entrapped into a polycationic calix[4]arene spontaneously self-assembling in micellar nanoaggregates. The calixarene-based nanoconstructs as nanocontainers and nanocarriers enhanced solubility and local concentration of the photodonors and as a nanoreactor increased the release of NO under the exclusive control of visible light inputs. The light-stimulated bactericidal effect was successfully tested on Gram positive and Gram negative bacteria.