Confinement of Therapeutic Enzymes in Selectively Permeable Polymer Vesicles by Polymerization-Induced Self-Assembly (PISA) Reduces Antibody Binding and Proteolytic Susceptibility

Covalent PEGylation of biologics has been widely employed to reduce immunogenicity, while improving stability and half-life in vivo. This approach requires covalent protein modification, creating a new entity. An alternative approach is stabilization by encapsulation into polymersomes; however this typically requires multiple steps, and the segregation requires the vesicles to be permeable to retain function. Herein, we demonstrate the one-pot synthesis of therapeutic enzyme-loaded vesicles with size-selective permeability using polymerization-induced self-assembly (PISA) enabling the encapsulated enzyme to function from within a confined domain. This strategy increased the proteolytic stability and reduced antibody recognition compared to the free protein or a PEGylated conjugate, thereby reducing potential dose frequency and the risk of immune response. Finally, the efficacy of encapsulated l-asparaginase (clinically used for leukemia treatment) against a cancer line was demonstrated, and its biodistribution and circulation behavior in vivo was compared to the free enzyme, highlighting this methodology as an attractive alternative to the covalent PEGylation of enzymes

Evaluating nature-based solution for flood reduction in spercheios river basin under current and future climate conditions

Nature-based solutions (NBS) are being deployed around the world in order to address hydrometeorological hazards, including flooding, droughts, landslides and many others. The term refers to techniques inspired, supported and copied from nature, avoiding large constructions and other harmful interventions. In this work the development and evaluation of an NBS applied to the Spercheios river basin in Central Greece is presented. The river is susceptible to heavy rainfall and bank overflow, therefore the intervention selected is a natural water retention measure that aims to moderate the impact of flooding and drought in the area. After the deployment of the NBS, we examine the benefits under current and future climate conditions, using various climate change scenarios. Even though the NBS deployed is small compared to the rest of the river, its presence leads to a decrease in the maximum depth of flooding, maximum velocity and smaller flooded areas. Regarding the subsurface/groundwater storage under current and future climate change and weather conditions, the NBS construction seems to favor long-term groundwater recharge. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Confinement of Therapeutic Enzymes in Selectively Permeable Polymer Vesicles by Polymerization-Induced Self-Assembly (PISA) Reduces Antibody Binding and Proteolytic Susceptibility

Covalent PEGylation of biologics has been widely employed to reduce immunogenicity, while improving stability and half-life <i>in vivo</i>. This approach requires covalent protein modification, creating a new entity. An alternative approach is stabilization by encapsulation into polymersomes; however this typically requires multiple steps, and the segregation requires the vesicles to be permeable to retain function. Herein, we demonstrate the one-pot synthesis of therapeutic enzyme-loaded vesicles with size-selective permeability using polymerization-induced self-assembly (PISA) enabling the encapsulated enzyme to function from within a confined domain. This strategy increased the proteolytic stability and reduced antibody recognition compared to the free protein or a PEGylated conjugate, thereby reducing potential dose frequency and the risk of immune response. Finally, the efficacy of encapsulated l-asparaginase (clinically used for leukemia treatment) against a cancer line was demonstrated, and its biodistribution and circulation behavior <i>in vivo</i> was compared to the free enzyme, highlighting this methodology as an attractive alternative to the covalent PEGylation of enzymes