Gadolinium Nanoparticles: Emerging Platforms Beyond Imaging for Drug Delivery and Theranostics

Gadolinium nanoparticles (GdNPs) have gained increasing attention as multifunctional metal-based nanoplatforms that extend far beyond their traditional use as magnetic reso-nance imaging (MRI) contrast agents. Their specific magnetic properties, tunable physicochemical features, and tunable biocompatibilities with biocompatible coatings give them great potential as drug delivery and theranostic applica-tions. They offer better stability, less systemic toxicity, and more surface modification options compared to molecular gadolinium chelates. Thermal decomposition, hydrothermal synthesis, polyol-based processes, and green methodologies, along with functionalization products that employ polymers, peptides, or targeting ligands, have significantly enhanced colloidal stability as well as biodistribution and selective accumulation at disease sites. Func-tionalized GdNPs exhibit outstanding properties not only as drug carriers for their specific indications but also as agents for multiple imaging modalities with superior therapeutic efficacy through radiosensitization and magneti-cally assisted delivery. Conjugation with ligands consisting of RGD peptides, hyaluronic acid, or folic acid allows receptor-mediated targeting and en-hances the uptake into cellular tissue in tumors. It is also important to men-tion that GdNP-based formulations have been proved to exert synergistic ef-fects when administered in combination with chemotherapeutic agents like doxorubicin, paclitaxel, and cisplatin. Although GdNPs have shown inter-esting preclinical findings, clinical translation of the products is limited due to scale-up limitations, long-term safety challenges, pharmacokinetics, and regulatory problems. This review presents synthetic strategies for the use of GdNPs, their main physicochemical and magnetic properties, ligand engi-neering for targeted delivery, and underlying biological mechanisms of their theranostic performance.