Engineering intrinsically radiolabeled nanoparticles for imaging and therapy: a decade of design strategies and insights.

The convergence of nanotechnology and nuclear medicine has opened new possibilities for cancer imaging and therapy, but conventional chelator-based radiolabeling approaches often suffer from limited stability and can alter the inherent properties of nanomaterials. Intrinsic radiolabeling has emerged as a promising alternative, enabling the direct incorporation of radionuclides within the nanoparticle matrix through mechanisms such as lattice doping, isotopic substitution, coordination to structural sites, or entrapment during nanoparticle formation. In this approach, the radionuclide becomes an integral part of the material architecture, thereby improving radiochemical stability while preserving the intrinsic physicochemical properties of the nanomaterial. Emphasis is given to how rational design and synthetic strategies have evolved to address key challenges in stability, scalability, and biological performance. A range of nanoplatforms-including inorganic systems, protein-based hybrid nanoparticles, and biomaterial-assisted systems such as hydroxyapatite and polymers-are discussed to illustrate the diversity of approaches explored. Particular attention is devoted to methodologies such as