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Polymeric Cyclodextrin-Based Supramolecular Constructs Photoreleasing Nitric Oxide for Combating Antibiotic Resistance

Project description

A supreme weapon against antibiotic resistance

Multi-drug resistant (MDR) bacteria emerge from the accumulation of multiple genes conferring resistance to different antibiotics. These microorganisms pose a serious medical challenge, threatening the outcome of simple surgeries and infections. Funded by the Marie Skłodowska-Curie Actions programme, the SUPREME project aims to develop an innovative therapeutic approach against MDR bacteria using nitric oxide (NO). NO is implicated in immune reactions against various pathogens and also inhibits drug efflux pumps responsible for multi-drug resistance. Researchers will develop a sophisticated nanosystem that responds to light to release the therapeutic cargo such as antibiotics and NO.

Objective

With more than 13 million people dying per year from infectious diseases Multidrug Resistance (MDR) in bacteria remains the
greatest challenge in public health care. This scenario, associated to the low turnover of new clinically approved antibiotic
drugs makes the development of innovative therapeutic approaches to fight antibiotic resistance desperately needed to
address this devastating societal problem. In this frame, SUPREME aims at the implementation of a novel strategy based
on unprecedented supramolecular platforms based on new cyclodextrin polymers integrating light-activatable nitric oxide (NO)
photodonors (NOPD), alone and in combination with antibiotics currently employed in the clinic. The final goal is to exploit
the double role of NO generated with superb spatiotemporal control thanks to the light triggering, as: i)
bactericidal species not suffering MDR when produced at high doses (micro molar); ii) inhibitor of the efflux pumps mainly responsible
for MDR, when produced at low doses, to revert antibiotic resistance. Highly biocompatible branched polymers containing mixed (alpha, beta and gamma) cyclodextrin units will be used as suitable hosts able to self-assemble into nanoparticles or gels
encapsulating the therapeutic cargo with high efficiency. We will focus on NOPDs activatable exclusively with the
biocompatible visible light and on antibiotics representative of the classes of fluoroquinolones and
tetracyclines, known to display resistance and severe side effects. Full chemico-physical and photochemical characterization
of the systems is planned as well as assessment of their efficacy against planktonic microbial cells and biofilms. The complementary
expertise of the researcher and the supervisor supported by the private and academic teams hosting the fellow during
secondments will create a multidisciplinary environment where all participants will benefit from reciprocal transfer of
knowledge.

Coordinator

UNIVERSITA DEGLI STUDI DI CATANIA
Net EU contribution
€ 172 750,08
Address
PIAZZA UNIVERSITA 2
95131 Catania
Italy

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Region
Isole Sicilia Catania
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (2)