Rational design and preclinical evaluation of elastin-like polypeptide micelle nanoparticles for drug delivery

Elastin-like polypeptide (ELP) micelle nanoparticles have emerged as versatile and tunable platforms for drug delivery across diseases. These bio-inspired and thermo-responsive polymers typically produced recombinantly in E.coli or yeast offer great biocompatibility, low immunogenicity, and cost-effective production. Rationally designed amphiphilic diblock ELPs, ELP-drug/polymer/protein conjugates, and ELP-nucleic acid polyplexes can self-assemble into micelle or micelle-like nanoparticles at physiological temperatures. Similar to other nanoparticle drug delivery systems, ELP micelles can load a broad range of drugs, prolong systemic circulation, and enable controlled and sustained drug release. Notably, ELP micelles provide unique advantages for delivering protein and peptide drugs, as their conjugates with ELP can be recombinantly synthesized with a 100% conjugation efficiency, eliminating the need for chemical coupling. In this review, we will discuss the design principles of ELP micelle-based drug delivery systems and summarize their recent applications in cancer therapy and vaccine development.