Development of sustainable nanomaterials for the purification of antileukemic drugs

Abstract

Getting older is the biggest risk factor for most fatal diseases, including cancer, heart disease and Alzheimer's. The advances in nanomedicine comprise the development of nanoparticles either for drug delivering or as platforms for biomolecules purification. Simultaneously, continuous progresses have been made for the development of recombinant therapeutic enzymes, namely L-asparaginase (LA), which presents antineoplastic properties for thetreatment of leukaemia's, in particular for Acute Lymphoblastic Leukemia (ALL). Currently, the LA available in medicalapplications is produced from bacteria. However, this type of LA may activate the immunological system causinghuman hypersensitivity reactions. Therefore, the search for novel microorganisms able to produce LA with no sideeffects has been the main focus of many researches.Considering the great demand for the development of new technologies for the purification of therapeutic enzymes,still limited by their high cost, this project aims to produce recombinant LA by bacteria fermentation and to developa cost-effective and sustainable platform for the biopharmaceutical purification (downstream processing) from the fermentation broth using nanomaterials. The main goal is to obtain recoveries of LA above 90% and purity levels over95%, with a cost reduction around 20%. A critical evaluation of the best strategies and conditions for the integrationprocesses and scale-up will be explored. The involved research teams (CICECO, FEUP and UNESP) have shownto be successful in providing pioneering scientific results on the production of enzymes and on the developmentof separation and purification techniques for biopharmaceuticals. The UNESP team from Brazil will optimise noveltechniques of heterologous enzyme production by bacterial fermentation, which is generally regarded as safe (GRAS)and easy to manipulate, in order to achieve higher enzyme yields. The Portuguese teams (CICECO and FEUP) willbe responsible for the preparation of functionalisation of silica and carbon nanomaterials, which will be used as anefficient and fast strategy for LA purification from the fermentation medium. NanoPurAsp aims to meet the approval of biopharmaceuticals by regulatory authorities which require effective andhigh quality biopharmaceuticals, i.e., no side-effects, high purity and biological activity. These can only be attained through in-depth knowledge of the products and of their manufacturing processes. The advanced research here produced will certainly allow the success of therapeutic enzymes production and its easy scalability up to industrial levels at a lower cost. The integrated process developed will have a great impact in economy with a long-term impact in human healthcare. This project aspires the optimization of resources and materials which will contribute to a greener and sustainable growth, which in turn will be a source of economic valorisation for the future industrial manufacturing. (AU)