Nano-functionalized natural killer cells for thyroid disease: Emerging concepts, translational barriers, and future perspectives

Thyroid disorders, including benign goiter, autoimmune thyroid diseases, and thyroid malignancies, continue to present significant clinical challenges despite advances in surgical, pharmacological, and radioiodine-based treatments. Recent developments in nanomedicine and immune-cell engineering have generated interest in the use of natural killer (NK) cells as therapeutic and drug-delivery platforms for targeted disease management. However, the potential application of NK cell–nanoparticle hybrid systems in thyroid disorders remains largely exploratory and requires careful evaluation of their biological rationale, therapeutic feasibility, and translational limitations. This review critically examines current advances at the interface of NK-cell engineering and nanotechnology, with particular emphasis on their potential relevance to thyroid diseases. We discuss established NK-cell-based strategies, including chimeric antigen receptor (CAR)-NK cells, membrane engineering, and nanoparticle-assisted functional enhancement, alongside nano-enabled delivery systems such as polymeric nanoparticles, liposomes, and extracellular vesicle-inspired platforms. Particular attention is given to thyroid cancer and immune-mediated thyroid disorders, where immune-targeted interventions may have greater mechanistic justification than benign thyroid enlargement. Available preclinical evidence is reviewed, and distinctions are made between experimentally validated approaches and hypothetical future applications. In addition, we critically assess major challenges associated with NK cell–nanoparticle hybrid technologies, including targeting specificity, biodistribution, immunogenicity, manufacturing scalability, storage stability, safety considerations, and regulatory requirements for clinical translation. By integrating evidence from immunotherapy, nanomedicine, and thyroid disease research, this review identifies current knowledge gaps, evaluates the realistic therapeutic potential of NK-cell-enabled nanoplatforms, and outlines future research priorities necessary for their successful clinical development. Rather than proposing immediate clinical implementation, we provide a balanced assessment of the opportunities and limitations of NK-cell nanoengineering as a prospective strategy for precision treatment of selected thyroid disorders.