Genetically engineered elastin-like polypeptide nanoparticles for enhanced protein delivery and therapeutic
1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 511442, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guangdong 510006, China; Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, Guangdong 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong 510006, China.
None:
Protein therapeutics offer high specificity and potency but face clinical limitations such as poor stability, rapid clearance, and suboptimal patient compliance. To address these challenges, we engineered an elastin-like polypeptide (ELP)-based delivery system by genetically fusing the N-terminal domain of Annexin A1 (ANXA1-N) with ELP to generate ANXA1-N-ELP fusion proteins. These proteins self-assembled into nanoparticles at physiological temperature, preserving ANXA1-N activity while markedly improving its pharmacokinetics. The resulting nanoparticles exhibited homogeneous composition, prolonged circulation, and favorable biodistribution. Both in vitro and in vivo studies further confirmed their potent anti-inflammatory activity. In a murine model of inflammatory bowel disease (IBD), ANXA1-N-ELP treatment effectively alleviated inflammation, restored immune homeostasis, and improved disease outcomes. Importantly, the fully genetically encoded ELP carrier enables precise molecular design, tunable biophysical properties, and controlled biosynthesis. Collectively, this study establishes a versatile protein delivery platform with significant therapeutic potential for IBD and other inflammation-related disorders, advancing the clinical translation of protein-based therapeutics.
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