Broadening Approaches in Nanoparticle Synthesis Through Elastin-Like Polypeptides

Research is continuously searching for new knowledge niches or technical developments that could have a societal impact and game-changing fundamental findings. Since the biomedical field entangles several disciplines, a particular problem is tackled from different approaches which helps to develop new solutions that can crystallize in biomedical devices with applications in diagnosis, therapy or theranostics. Certainly, the properties of the materials under study govern the scope of the biomedical research, e.g., quantum dots (QDs) and its fluorescence properties for imaging and detection or magnetic nanoparticles (NPs) for magnetic resonance imaging (MRI) and hyperthermia. In this sense, elastin-like polypeptides (ELPs) are not different and their capability to assemble into nanoparticles by themselves has naturally attracted most of the attention for their use in biomedical devices. Therefore, less efforts have been made in their application in NP synthetic procedures. ELPs are genetically engineered repetitive proteins derived from tropoelastin. Their thermoresponsive properties allows the formation of supramolecular structures by phase separation in a reversible fashion. In aqueous solvents below their transition temperature (Tt) they are solubilized, while above Tt they acquire hydrophobic character and collapse causing the segregation. This reversible conformational change from random coil to primarily type-II β-turns leads to the formation of a coacervates (Löwik et al., 2010). The Tt or lower critical solution temperature (LCST) is defined by the hydrophilic/hydrophobic balance of the amino acid sequence (VPGXG), were X can be any residue except proline (Varanko et al., 2020). 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). This drug-polypeptide conjugate was able to form 100 nm nanoparticles and deliver their chemotherapeutic payload in a murine cancer model, inducing an almost completely tumor regression after a single dose. ELPs engineering also can serve as a straightforward way to incorporate protein-based targeting agents or encapsulate the protein of interest with high efficiency (van Oppen et al., 2019; Pille et al., 2021). Since inorganic nanoparticle synthetic processes are varied but needed for physiological stabilization in biomedical applications, one may expect that ELPs have been widely applied as NP coatings. Instead, best examples of organic-inorganic hybrid materials based on elastin-like polypeptides found in the fabrication Edited by: Guocheng Wang, Shenzhen Institutes of Advanced Technology (CAS), China