Designer protein delivery: From natural to engineered affinity-controlled release systems

Abstract

Exploiting binding affinities between molecules is an established practice in many fields, including biochemical separations, diagnostics, and drug development; however, using these affinities to control biomolecule release is a more recent strategy. Affinity-controlled release takes advantage of the reversible nature of noncovalent interactions between a therapeutic protein and a binding partner to slow the diffusive release of the protein from a vehicle. This process, in contrast to degradation-controlled sustained-release formulations such as poly(lactic-co-glycolic acid) microspheres, is controlled through the strength of the binding interaction, the binding kinetics, and the concentration of binding partners. In the context of affinity-controlled release--and specifically the discovery or design of binding partners--we review advances in in vitro selection and directed evolution of proteins, peptides, and oligonucleotides (aptamers), aided by computational design.

Affinity-controlled protein encapsulation into sub-30 nm telodendrimer nanocarriers by multivalent and synergistic interactions

“…We would like to emphasize that the protein release rate by serum protein exchange can vary for different cargo proteins and can be tailored by engineering the relative binding affinity of telodendrimer to the cargo protein. [19] For example, insulin, a pH-low insertion peptide (pHLIP-Alxa750-DOX)[45] conjugated with doxorubicin and a near infrared dye Alexa750, and granulocyte-colony stimulating factor (GCSF) loaded in the telodendrimer NPs were very stable against BSA incubation at a biological concentration of 40 mg/mL (Fig. S26–S29), indicating strong binding affinity between these cargo proteins and telodendrimers.…”

“…Recently, protein-binding moieties have been introduced into hydrogel systems for further control of protein release based on the affinitive binding and dissociation. [17–19]…”

“…[19] However, such well-defined interactions are hard to be implanted in polymer nanocarriers for protein encapsulation, due to the monotonic feature of conventional polymer chemistries. Alternatively, Xu and coworkers have demonstrated that the structures and properties of both charged head groups and hydrophobic tails in the positively charged surfactant are important for efficient protein absorption and intracellular delivery using these surfactant nanoparticles (NPs) stabilized by phospholipids/cholesterol and polyethylene glycol-lipid (PEG-lipid).…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…If the system is reversed whereby SH3-binding peptides are coexpressed with proteins and SH3 covalently bound to the hydrogel, controlled release of multiple proteins with independent release rates will be dictated by the unique SH3-binding peptide on each fusion protein (Delplace et al, 2016). Advances in computational design of protein-protein interactions and phage display libraries will increase the variety of binding interactions available for affinity release strategies, increasing their utility (Pakulska et al, 2016b). Recently, innovative work has used electrostatic interactions to control drug release from PLGA particles without the need for encapsulation (Pakulska et al, 2016a).…”

Bioresponsive Materials for Drug Delivery Based on Carboxymethyl Chitosan/Poly(γ-Glutamic Acid) Composite Microparticles

“…An ideal drug delivery system should be able to increase drug solubility, provide a sustained release system to avoid rapid breakdown and excessive use, and improve biodistribution [1]. Mild reaction conditions and absence of toxic or/and active organic substances are required to maintain the activity of active drugs, such as proteins [2,3]. Controlled-release systems based on smart bioresponsive materials have been extensively studied to delivery drugs [4].…”