Bio-Inspired Smart Elastin-Like Polypeptides (ELPs) for Precision Drug Delivery: Molecular Strategies, Thermal...

Elastin-like polypeptides (ELPs), inspired by the natural elasticity of human elastin, are rapidly evolving as next-generation platforms for precision drug delivery. Their unique thermoresponsive behavior, genetic tunability, and biocompatibility position them at the intersection of molecular engineering and translational medicine. In this perspective, we critically examine the design strategies that shape ELP functionality, ranging from sequence-level engineering and guest residue modulation to fine-tuning of the inverse transition temperature (T_t). We highlight how these molecular design principles enable programmable self-assembly into nanostructures such as micelles and nanogels, creating versatile opportunities for both covalent and non-covalent cargo encapsulation. Beyond conventional drug delivery, ELPs are poised to transform therapeutic modalities through hyperthermia-guided targeting, multi-stimuli responsiveness, and co-delivery systems that integrate nucleic acids, siRNA, and CRISPR-based components. We also explore emerging frontiers in ELP-enabled immunotherapies, theranostic platforms, and personalized medicine, while reflecting on translational challenges, regulatory landscapes, and the growing role of artificial intelligence in accelerating ELP design. Also, we argue that ELPs are not merely biomaterials but dynamic molecular tools capable of redefining precision therapeutics, and we outline key opportunities that will shape their path toward clinical impact.