Genetically Encoded Elastin‐Like Polypeptides for Drug Delivery

Abstract

Elastin‐like polypeptides (ELPs) are thermally responsive biopolymers that consist of a repeated amino acid motif derived from human tropoelastin. These peptides exhibit temperature‐dependent phase behavior that can be harnessed to produce stimuli‐responsive biomaterials, such as nanoparticles or injectable drug delivery depots. As ELPs are genetically encoded, the properties of ELP‐based biomaterials can be controlled with a precision that is unattainable with synthetic polymers. Unique ELP architectures, such as spherical or rod‐like micelles or injectable coacervates, can be designed by manipulating the ELP amino acid sequence and length. ELPs can be loaded with drugs to create controlled, intelligent drug delivery systems. ELPs are biodegradable, nonimmunogenic, and tolerant of therapeutic additives. These qualities make ELPs exquisitely well‐suited to address current challenges in drug delivery and have spurred the development of ELP‐based therapeutics to treat diseases—such as cancer and diabetes—and to promote wound healing. This review focuses on the use of ELPs in drug delivery systems.

Polymer-Based Delivery of Peptide Drugs to Treat Diabetes: Normalizing Hyperglycemia and Preventing Diabetic Complications

“…Significant efforts have been invested to identify potential peptide drugs to treat diabetes, including insulin, GLP-1, FGF21, proinsulin C-peptide, and apelin [3,12,13,56]. However, a key limitation of most naturally occurring peptides for clinical uses is their short circulating half-life due to their poor stability, proteolysis, and rapid renal clearance [12].…”

“…Fatty acylation also extend the half-lives of peptide drugs by interaction of fatty acid with albumin that enables the peptide to dissociate from albumin in circulation and retain its potency [12]. Another approach is to yield controlled-releasable products of peptide drugs by fusion with biopolymers, including elastin-like polypeptides (ELP) [11][12][13]. In this section, we discuss the delivery of peptide drugs to normalize blood glucose levels and prevent diabetic complications for the treatment of diabetes.…”

“…However, the key limitation of the peptide drugs for the treatment of diabetes is their short halflife [7,9,11]. To overcome this limitation, significant efforts have been made by various researchers to synthesize longer acting analogs to extend their blood circulating times, using conjugation with biopolymers, polyethylene glycol (PEG) ylation, and fatty acylation [6,[11][12][13][14]. Moreover, clinical trials demonstrated that blood glucose normalization does not prevent diabetic complications caused by hyperglycemic memory (HGM) [15][16][17].…”

Construction of protein nanoparticles for targeted delivery of drugs to cancer cells

“…Elastin like polypeptides (ELPs) are often used in the design of drug delivery carriers, owing to their biocompatibility, biodegradability, and drug loading capacities. [1][2][3] Another valuable characteristic of ELPs is their formation of temperature-dependent aggregates, called coacervates, above a specific transition temperature. 4,5 However, ELP aggregates are too large to allow for their use as drug carries.…”

Broadening Approaches in Nanoparticle Synthesis Through Elastin-Like Polypeptides

“…This property has been widely used for recombinant protein solubilization and purification in which the protein of interest is elongated with an ELP polypeptide and then subjected to an inverse transition cycling (ITC) procedure to separate the target protein from the lysate products (Fletcher et al, 2019). Since the building blocks of ELPs are natural amino acids, their biocompatibility, biodegradability, and non-immunogenicity make them even more attractive for applications in tissue engineering or nanomedicine (Jenkins et al, 2021). One of the first examples of their application in the nanomedicine field was carried out by Chilkoti laboratory, where the introduction of a cysteinecontaining segment allowed the conjugation of a doxorubicin derivative through a pH cleavable linker (Andrew MacKay et al, 2009).…”