Finite-Capacity Corona Governance: Body Fluids as Biological Identity-Assignment Systems for Nanoscale Interfaces

Nanoscale therapeutics, lipid nanoparticles, extracellular vesicles and other particle-like interfaces are usually designed as material objects, but they rarely meet biological readers as pristine surfaces. After entering blood, lymph, interstitial fluid or inflammatory exudates, they are rapidly rewritten by adsorbed, exchanged and modified biomolecules. Protein-corona research has established that this host-conditioned layer can define biological identity, yet the field still lacks a framework for asking a more demanding question: under what conditions can a body fluid maintain a transport-compatible identity for an incoming interface, and when does that assignment shift toward clearance, complement activation, coagulation, inflammation or delivery failure? This Hypothesis proposes finite-capacity corona governance as a testable framework in which protein-rich body fluids function as biological identity-assignment systems with local, finite and disease-sensitive functional capacity. The framework contains two mechanistic claims and one causal attribution standard. First, under matched particle-core conditions, different physiological or pathological fluids assign reproducible surface-accessible corona identity states. Second, for a defined particle class, fluid state and exposure condition, increasing accessible surface-area burden generates a measurable capacity curve; in vulnerable fluids, specific reader modules may undergo nonlinear switching from shielding or transport-associated identities to opsonin-, complement-, coagulation- or instability-associated identities. Because corona composition alone cannot establish causality, the framework further imposes a gatekeeping standard: a fate output should be called corona-governed only when the retained particle-bound identity transfers with washed particles into a common reader system, remains sensitive to label depletion or rescue, and depends on the predicted biological reader. The proposed metric, C_cap,p,f,e,m = S_crit,p,f,e,m / V_fluid, is not a universal plasma constant but a particle-fluid-exposure-specific functional threshold defined for a pre-specified reader module. This framework is intentionally falsifiable: it would be narrowed if response curves remain purely linear, if disease-fluid effects disappear after soluble-factor control, or if fate is better explained by aggregation, material toxicity, payload pharmacology or reader-independent mechanisms. If supported, finite-capacity corona governance would shift nano-bio interface research from asking only what corona forms to asking how host fluids assign biological identity, how much interface burden that assignment can tolerate, when disease states lower this functional reserve and what causal evidence is required before an altered fate can be attributed to the particle-bound corona.