Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 2 2026 06 15 Translational Landscape of Nanopharmaceuticals: Progress and Prospects on Biomacromolecule Delivery and Active Targeting 206 212 10.34172/apb.47355 EN Azam Safary https://orcid.org/0000-0002-8997-2003 Mostafa Akbarzadeh-Khiavi https://orcid.org/0000-0002-1552-6537 EDITORIAL 10.34172/apb.47355 2026 04 08 2026 05 07 Over the past two decades, nanopharmaceuticals have demonstrated strong potential for biomacromolecule delivery, yet clinical translation remains scarce. This study examines the persistent gap between laboratory research and clinical application, drawing on practical lessons from enzyme-conjugated nanoparticles, EGFR-targeted gold nanoparticles, and magnetic nanobiosystems. Although multifunctional nanocarriers excel in vitro, their clinical success is often hindered by biological factors that are frequently neglected in laboratory studies. These issues include protein corona formation, which diminishes targeting specificity; complexities in optimizing ligand density; challenges in scaling up manufacturing; and regulatory hurdles. The protein corona, forming immediately after biological exposure, fundamentally alters nanoparticle identity and targeting in clinical environments. Moreover, complex multi-component designs often fail to translate due to batch variability and excessive production costs. This study advocates prioritizing design principles that emphasize manufacturability, biological robustness, and regulatory practicality over technological novelty. By applying insights from two decades of translational barriers, the field can advance toward clinically viable nanopharmaceutical platforms through simplified designs that address real-world limitations.