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.

Nanomedicine recognition and clearance by the mononuclear phagocyte system (MPS) impedes optimal clinical impacts for this class of materials. We present an overview of factors involved in MPS interactions and approaches to overcome this barrier.

We report the design of an α-helical peptide that forms self-healing hydrogels at weight fractions below 0.1%. Gelation of the 21-residue peptide AFD19 is controlled by changes in pH, whereby highly-charged peptide states give low-viscosity solutions, while thermostable gels form at pH values where the peptide charge lies close to +1 or −1. At pH values where the molecular charge approaches zero, the peptide forms insoluble fibrils. Transitions between the liquid, gel and insoluble states of the peptide are reversible upon addition of acid or base. Electron microscopy, dynamic light scattering and electronic circular dichroism studies indicate that gelation occurs when the peptide self-assembles into soluble coiled-coil fibrils that form cross-links below a critical zeta potential. The formation of extended fibrils occurs in the absence of any explicit design to drive helix offsetting.