Nanotechnological Approaches to Therapeutic Delivery Using Elastin-Like Recombinamers

Abstract

This review discusses the use of elastin-like polymers and their recombinant version, elastinlike recombinamers, in drug-delivery systems. These macromolecules exhibit a number of interesting properties that are rarely found together in any other family of materials, especially extremely high biocompatibility, high bioactivity and functionality, complex yet fully controlled composition and stimuli responsiveness.Appropriate design of these molecules opens up a broad range of different possibilities for their use in new therapeutic platforms. The first of these described herein is the use of ELRs in singlemolecule devices as therapeutic entities on their own. Subsequently, we describe how the selfassembly properties of these materials can be exploited to create nanocarriers and, eventually, microcarriers that are able to temporally and spatially control and direct the release of their drug load. Intracellular drug-delivery devices and nanocarriers for treating cancer are among the uses described in that section. Finally, the use of ELRs as base materials for implantable drug depots, in the form of hydrogels, is discussed.

A double safety lock tumor-specific device for suicide gene therapy in breast cancer

“…In addition, tumor-specific promoters provide a safe and effective strategy for designing gene-therapy systems that can be adapted for use with various tumors or delivery systems. To date, ELRs and other polymers widely used as non-viral vectors, such as poly-lysine (PLL), polyethylenimine (PEI), polyethyleneglycol (PEG), chitosan, poly(lactic-co-glycolic acid) (PLGA), or poly(2-dimethylaminoethyl methacrylate) (pDMAEMA) [20], have found increasing applications in biomedicine due their inherent biocompatibility and smart properties [21][22][23][24][25][26][27][28][29]. A previous study showed the ability of ELRs joined to functional peptides to be used as delivery vectors with no cellular effects in vitro [30].…”

Trends in the design and use of elastin-like recombinamers as biomaterials

“…Furthermore, we will comment the diverse applications inferred from the control of their ordered-disordered state. Moreover, while several publications have already reviewed the use of ELRs in drug delivery [20,21] and in tissue engineering and regenerative medicine (TERM) [1,[22][23][24], herein we will point out the major advances in the multi-purpose design and use of ELRs in these fields in the past few years. Finally, we will describe other designs and applications that do not completely fit into the aforementioned sections.…”

Novel Hydrogel-forming elastin-like recombinamers for biomedical applications

“…In tissue engineering, hydrogels have been the predominant matrices for application in the human body in the last 40 years (165,(188)(189)(190). ELRs are non-immunogenic, and according with their biodegradability and biocompatibility for human tissue, blood, and other fluids, they can play a key role as carriers in delivery systems (189,191,192).…”

“…Furgerson's group to deliver an EGFP−plasmid inside cells in in vitro assays (193). The use of specifically designed ELRs joined to functional peptides as agents shows promising results for delivering genes in vitro (190). Moreover, cellular transfection can be improved through the formation of charged polyplexes and their further interaction with the negatively charged components on the cell membrane, such as proteoglycans and cell-surface receptors (194,195).…”

“…In this study, taking advantage of the recombinant DNA technology to design and produce ELRs, functional motifs were incorporated into a basic ELR sequence. Then, imidazole groups were covalently bound, obtaining stable polyplexes composed of plasmid DNA and ELRs (190). Several studies have demonstrated the use of ELRs fused to a cell penetrating peptide (CPP) as a drug delivery vector for solid tumors (182,196,197).…”