Carbonized Polymer Dots as Versatile Nanocarrier for Bioincompatible Fluorophore Imaging

Abstract Fluorophores with excellent emission often come at the cost of cell permeability, and this long‐standing dilemma has limited their effective applications in fluorescence bioimaging to some degree. We report a paradigm‐shifting discovery that carbonized polymer dots (CPDs) can function as a versatile, noncovalent translocation platform for a vast spectrum of otherwise impermeable fluorophores. Our investigation began with the serendipitous observation that a new molecule, 1‐(2‐hydroxyethyl)‐5‐oxo‐1,2,3,5‐tetrahydroimidazo[1,2‐a]pyridine‐7‐carboxylic acid (HECA), forms a stable, cell‐permeable nanocomplex with carbonized polymer dots (CPDs‐280) via noncovalent interactions (loading capacity ∼50.8%). This prompted a systematic exploration, which revealed that CPDs‐280 possess a remarkable capacity to override the innate targeting signals of diverse organelle‐specific dyes, rerouting them to the cytosol and demonstrating a carrier‐dominated localization mechanism. The platform's generality was rigorously proven by delivering custom‐designed, membrane‐impermeable amphiphilic dyes (ESY‐Na + and ESY), which remained inert alone but produced intense intracellular luminescence upon noncovalent complexation. This robust, cargo‐agnostic delivery capability is rooted in the abundant orthogonal anchor domains on the CPD's surface, enabling multimodal binding without chemical modification. This work unveils a generic strategy to breach biological barriers, instantly unlocking the vast repository of underutilized fluorescent probes for advanced bioimaging and theranostics.