Protein based biomaterials for therapeutic and diagnostic applications

Abstract

Proteins are some of the most versatile and studied macromolecules with extensive biomedical applications. The natural and biological origin of proteins offer such materials several advantages over their synthetic counterparts, such as innate bioactivity, recognition by cells and reduced immunogenic potential. Furthermore, proteins can be easily functionalized by altering their primary amino acid sequence and can often be further self-assembled into higher order structures either spontaneously or under specific environmental conditions. This review will feature the recent advances in protein-based biomaterials in the delivery of therapeutic cargo such as small molecules, genetic material, proteins, and cells. First, we will discuss the ways in which secondary structural motifs, the building blocks of more complex proteins, have unique properties that enable them to be useful for therapeutic delivery. Next, supramolecular assemblies, such as fibers, nanoparticles, and hydrogels, made from these building blocks that are engineered to behave in a cohesive manner, are discussed. Finally, we will cover additional modifications to protein materials that impart environmental responsiveness to materials. This includes the emerging field of protein molecular robots, and relatedly, protein-based theranostic materials that combine therapeutic potential with modern imaging modalities, including near-infrared fluorescence spectroscopy, single-photon emission computed tomography/computed tomography, positron emission tomography, magnetic resonance imaging, and ultrasound/photoacoustic imaging.

Computational Design of Homotetrameric Peptide Bundle Variants Spanning a Wide Range of Charge States

“…In addition to their central importance to the molecular basis of life processes, protein- and peptide-based systems have a wide range of applications to therapeutics, − food, − catalysts, − as well as nanoscale and macroscale materials. − Given that structure and function can often be encoded in the sequence of the amino acids, targeted properties can in principle be achieved via careful selection of sequences, solution conditions, and processing. Peptides have been used to engineer a wide range of assemblies, including nanotubes, nanosheets, nanolattices, and polymers of peptide building blocks. − The structure, functionality, and aggregation of proteins are a result of multiple noncovalent interactions, including electrostatic effects, hydrogen bonding, and hydrophobic interactions.…”

Biomaterials for Protein Delivery: Opportunities and Challenges to Clinical Translation

“…Though protein therapies are highly favored by researchers, they still face a hindering obstacle on the road toward clinical translation: efficient and targeted delivery mechanics. In nearly all cases, such therapies succeed because they both protect the protein's structure from degradation in order to ensure the protein's efficacy and simultaneously interact specifically with the corresponding target site in the body [2,24,125]. Although protein-based therapeutics show a high specificity at much lower concentrations than small-molecule drugs, integrating biomaterials into these therapeutic systems can help in overcoming difficulties through efficient and targeted delivery [8,126].…”

Fluorinated Protein and Peptide Materials for Biomedical Applications

“…The bioavailability of drug candidates is often the largest barrier from clinical translation as issues of solubility, aggregation, degradation, cell-membrane penetration, and clearance often necessitate a carrier molecule to protect and escort drug payloads to their targeted sites [ 79 ]. Accordingly, selection criteria for drug-delivering protein or peptide materials share many similarities with those employed for therapeutic use including easy administration, good pharmacokinetics and dynamics, and minimization of off-target effects; however, essential characteristics tend to be more flexible since the vehicle does not need to be intrinsically medicinal in nature [ 80 ]. This is often preferred so as not to confer unintended compounding effects.…”