Photosensitive polymersomes for anticancer cargo delivery

Abstract

ABSTRACT :Cancer is the second leading cause of death globally, occasioning 9,9 million deaths in 2020. This pathology significantly impacts the economy and lifestyle of cancer patients. Moreover, surgery, radiotherapy, and chemotherapy treatments present significant drawbacks related to their side effects, low specificity and selectivity, chemoresistance, and short drug lifetime. Hence, new alternatives to conventional therapies are necessary to overcome such limitations. Aiming to solve these issues, (nano)carriers such as polymersomes emerge promising, considering directed drug cargo release as an enhanced therapeutic approach. Therefore, mimicking nature vesicles' advantageous characteristics, cost-affordable bottom-up polymersomes are nanobioengineered as versatile compartmentalized systems for drug delivery. Beyond the protection and target delivery of therapeutics payloads by the compartmentalized structures, their function can be activated and boosted by external or internal stimuli that conduce to an "on-demand" releasing of the active components becoming accreditor of the "smart" adjective in the last decade. Among external stimuli such as ultrasound, temperature, or electric field, light constitutes a spatial-temporal innocuous controllable stimulus in broad wavelengths ranging from ultraviolet (UV) to near-infrared (NIR) light. On the other hand, electromagnetic radiation can trigger photochemical reactions, destabilizing the structures and releasing the payloads. The present work aims to develop a new photoresponsive polymersome based on poly(ethylene-altmaleic anhydride) and 2-nitrobenzyl alcohol for the on-demand cargo release of therapeutic agents against cancer. First, chapter I describes the theoretical information that encompasses polymer synthesis, characterization, assembly, functionalization, and biological performance. Then, it underlines light as an exogenous stimulus in smart light-responsive systems according to the effects on the polymeric structures with differentiated light-sensitive moieties upon electromagnetic irradiation in specific wavelengths. Additionally, it shows the state-of-the-art light-triggered polymersome-based anticancer therapeutics delivery systems depending on the light-mediated mechanism and subsequent processes. Chapter II reports the development of a new lightphotosensitive polymersome by wet chemical synthesis and self-assembly methods, physicochemical characterization, and evaluation as a multi-cargo delivery nanocarrier, including a dye, an anticancer drug, and inorganic nanoparticles. It shows polymersomes' with 75.01 ± 0.17 nm size, -50.94 ± 0.80 mV ζ-potential, and 3.45 ± 1.26 nm bilayer thickness. The light-responsive mechanism was studied following the polymeric membrane disruption after photolysis at 365 nm. Rhodamine-B and 5-Flurouracil were encapsulated into polymersomes with 20 and 14 % encapsulation efficiency and 3 and 5 % loading capacity, respectively, and the photo-mediated release of 5-FU was studied by spectroscopy encapsulation and controllable light-triggered release. Moreover, magnetite and gold nanoparticles were encapsulated into the polymersome hydrophilic core, suggesting the nanosystem's potential for theranostic duties. Finally, it covers preliminary data about polymersome functionalization and perspectives for further work.