Avian Eggshell Evolutionary Adaptations Inform Biomimetic Strategies for Next‑Generation Precision Cancer Theranostics

ABSTRACT

The avian eggshell is a sophisticated, multi‐functional biocomposite and, more importantly, an autonomous life‐support system evolved to safeguard embryonic development across dynamic and hostile environments. Discussing eggshell‐inspired biomaterials beyond simple structural imitation, this review translates these evolutionary survival strategies into functional biomimetic designs to address critical engineering bottlenecks in precision oncology. We systematically evaluate the biomineralization kinetics, porous architectures, and chemical selectivity of avian lineages nesting in extreme habitats, ranging from the hypercapnic geothermal burrows of megapodes to anthropogenically radiocontaminated landscapes. Drawing from these ecological paradigms, we summarize a framework for the engineering of eggshell‐inspired oncological theranostics based on three core mechanisms: the proton‐driven amorphous calcium carbonate (ACC) dissolution for spatiotemporally responsive cargo release within the acidic tumor microenvironment, the chelator‐free encapsulation of therapeutic radionuclides via Sr ^{2 +} /Ca ^{2 +} isomorphous lattice entrapment for targeted radiotherapy, and the repurposing of the antioxidant‐rich eggshell membrane (ESM) proteome to scavenge radiation‐induced reactive oxygen species (ROS) and mitigate collateral tissue damage. Ultimately, this review provides a standardized, bio‐inspired roadmap for designing next‐generation “nano‐egg” platforms, offering effective solutions to evade immune clearance, minimize off‐target toxicity, and overcome multidrug resistance, thereby providing valuable guidance for future biomimetic translation in oncology.