Advances in molecular design and synthetic chemistry enable the development of novel molecular therapeutic treatments of diverse diseases. A strategy proposed nearly 25 years ago for the treatment of metastatic cancer, but never realized, entails the following general processes: (i) Accumulation of an insoluble scaffold in the tumor extracellular space upon native enzyme (Enat) cleavage of a soluble precursor, and (ii) covalent attachment to the scaffold of a non-native (heterologous) enzyme (Ehet), which catalytically converts an abundance of aqueous-soluble radionuclide-bearing prodrug to an aqueous-insoluble drug; the latter precipitates in the tumor extracellular space. Here, the design and chemical synthesis of a molecular entity (1) for formation of the scaffold are described. Compound 1 is an “A2BC”-type lysine-based architecture that contains two chromogenic indoxyl-glucoside units (A), which upon cleavage by a glucosidase (Enat) undergo oxidative dimerization to provide a water-insoluble indigoid polymer; a maleimide (B) for attachment to a cancer-targeting agent; and the binding motif Loracarbef (C), a carbacephem antibiotic that forms a covalent adduct with a mutant β-lactamase (a proposed tether to, and/or possible fusion protein with, Ehet). Studies here also include maleimide–thiol conjugation of I to transferrin (a cell uptake carrier) and the covalent attachment of a mutant b-lactamase to Loracarbef. Together, the work supports an approach for molecular brachytherapy (or endoradiotherapy), where radionuclide seeds are self-assembled directly in the region of therapeutic need.