Elastin-Like Recombinamers As Smart Drug Delivery Systems

Arias, Francisco J.; Santos, Mercedes; Ibáñez‐Fonseca, Arturo; Piña, Maria J.; Serrano, Sofía

doi:10.2174/1389450117666160201114617

Cited by 14 publications

(11 citation statements)

References 152 publications

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“…Recombinant elastin-like polypeptides (ELPs) are usually produced in E. coli (Cappello et al, 1990; McPherson et al, 1992). There is considerable biomedical interest in these materials in view of their biocompatible properties (Urry et al, 1991b) and tunable transition temperature, with possible applications mainly in controlled drug delivery and tissue engineering (for reviews, see Arias et al, 2018; MacEwan and Chilkoti, 2010; Nettles et al, 2010). The yield of ELPs in E. coli was markedly improved by relying on leaky transcription by the T7 promoter and culturing for extended periods, rather than using standard isopropyl β-D-1-thiogalactopyranoside (IPTG) induction (Guda et al, 1995).…”

Section: Protein Polymers Produced In P Pastorismentioning

confidence: 99%

Production of protein-based polymers in Pichia pastoris

Werten

Eggink

Stuart

et al. 2019

Biotechnology Advances

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Materials science and genetic engineering have joined forces over the last three decades in the development of so-called protein-based polymers. These are proteins, typically with repetitive amino acid sequences, that have such physical properties that they can be used as functional materials. Well-known natural examples are collagen, silk, and elastin, but also artificial sequences have been devised. These proteins can be produced in a suitable host via recombinant DNA technology, and it is this inherent control over monomer sequence and molecular size that renders this class of polymers of particular interest to the fields of nanomaterials and biomedical research. Traditionally, Escherichia coli has been the main workhorse for the production of these polymers, but the methylotrophic yeast Pichia pastoris is finding increased use in view of the often high yields and potential bioprocessing benefits. We here provide an overview of protein-based polymers produced in P. pastoris . We summarize their physicochemical properties, briefly note possible applications, and detail their biosynthesis. Some challenges that may be faced when using P. pastoris for polymer production are identified: (i) low yields and poor process control in shake flask cultures; i.e. , the need for bioreactors, (ii) proteolytic degradation, and (iii) self-assembly in vivo . Strategies to overcome these challenges are discussed, which we anticipate will be of interest also to readers involved in protein expression in P. pastoris in general.

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Section: Protein Polymers Produced In P Pastorismentioning

confidence: 99%

Production of protein-based polymers in Pichia pastoris

Werten

Eggink

Stuart

et al. 2019

Biotechnology Advances

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“…In addition, their stimulus-responsive behaviour can be tuned as Tt is controlled by the amino-acid composition of the recombinamer. 12 Given their cell-friendly behaviour, tunable mechanical properties, thermal sensitivity, and ability to self-assemble, they are useful biomaterials for most applications in the fields of nanotechnology and biomedicine and, specifically, for controlled drug delivery. [13][14][15][16][17] Cancer is one of the potential applications of drug delivery systems as it is one of the most common diseases worldwide.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt

et al. 2019

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This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug delivery system based on elastin-like block recombinamers. The DNA recombinant technics allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH and blockage of cellular growth by a small peptide inhibitor. The recombinant polymer reversibly self-assembled, when temperature was increased above 15°C, into nanoparticles with a diameter of 72 nm and negative surface charge. Furthermore, smart nanoparticles were showed to enter in the cells via clathrin-dependent endocytosis, and properly blocked phosphorylation and consequent activation of Akt kinase. This system provoked apoptosis-mediated cell death in breast and colorectal cancer cells, which possess higher expression levels of Akt, whereas non-cancerous cells, such as endothelial cells, fibroblasts and mesenchymal stem cells, were not affected. Hence, we conclude that the conformational complexity of this smart elastinlike recombinamer leads to achieve successful drug delivery in targeted cells and could be a promising approach as nanocarriers with bioactive peptides in order to modulate multiple cellular processes involved in different diseases.

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“…Enormous efforts are still underway for developing novel and effective gene delivery systems based on biocompatible nanomaterials to transfer the target genes to the tumor site [167,191,192]. For example, researchers have developed an elastin-like recombinant (ELR) and specific MUC1 aptamers for intracellular delivery of the MUC1 gene to breast tumors [193].…”

Section: Breast Cancer Therapymentioning

confidence: 99%

In vivo gene delivery mediated by non-viral vectors for cancer therapy

Mohammadinejad

Dehshahri

Madamsetty

et al. 2020

Journal of Controlled Release

165

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Elastin-Like Recombinamers As Smart Drug Delivery Systems

Abstract: Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments.

Cited by 14 publications

References 152 publications

Production of protein-based polymers in Pichia pastoris

Production of protein-based polymers in Pichia pastoris

Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt

In vivo gene delivery mediated by non-viral vectors for cancer therapy

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