Construction and manipulation of metal-based supramolecular polymers-which are based on a combination of nucleobase hydrogen bonding interactions and functional metal ions-to obtain the desired physicochemical properties and achieve the efficacy and safety required for biomedical applications remain extremely challenging. We successfully designed and synthesized a new mercury-based supramolecular polymer, Hg-BU-PPG, containing an oligomeric polypropylene glycol backbone and pH-sensitive uracil-mercury-uracil (U-Hg-U) linkages. This multifunctional metallo-supramolecular material spontaneously self-organizes into nanosized spherical micelles in aqueous solution. The micelles possess several attractive properties, including desired long-term structural stability in serum-rich conditions, unique fluorescence behavior and highly sensitive, well-controlled pH-responsiveness. Interestingly, Hg-BU-PPG micelles exhibited strong, selective cytotoxic effects towards cancer cells in vitro, without harming normal cells. The highly selective cytotoxicity can be attributed to rapid dissociation of the U-Hg-U complexes within the micelles in the mildly acidic intracellular pH of cancer cells, followed by release of inherently toxic mercury ions. Importantly, fluorescence microscopy and flow cytometry clearly demonstrated that Hg-BU-PPG selectively entered the cancer cells via endocytosis and rapidly promoted massive apoptotic cell death. In contrast, internalization of Hg-BU-PPG by normal cells was limited, resulting in high biocompatibility and no cytotoxic effects. Thus, this newly discovered 'cytotoxicity-concealing' supramolecular system could represent a viable route to enhance the safety and efficacy of cancer therapy and bioimaging via a strategy that does not require incorporation of anticancer drugs and fluorescent probes. STATEMENT OF SIGNIFICANCE: We report a significant breakthrough in the construction of mercury-containing supramolecular polymers, namely the creation of multifunctional micelles with unique chemical and physical properties conferred by pH-sensitive uracil-mercury-uracil (U-Hg-U) linkages and tunable structural and dynamical features due to the presence of hydrogen-bonded uracil moieties. Importantly, in vitro experiments clearly demonstrated that introduction of the U-Hg-U complexes into the micelles not only improved the efficiency of selective uptake via endocytosis into cancer cells, but also accelerated the induction of massive apoptotic cell death. Thus, this work provides crucial new insight for the development of metallo-supramolecular polymeric micelles that may substantially enhance the safety and efficacy of cancer therapy and bioimaging without requiring incorporation of anticancer drugs or fluorescent probes.