Reactive oxygen species (ROS) and active alkylating chemotherapeutics are important bioanalytes but difficult to measure selectively, in vivo, or in real time. A new nanoscale optical sensor platform under development can detect as well as identify these analytes in situ. Carbon nanotube-DNA complexes, formed by individually encapsulating nanotubes with oligonucleotides, respond in real time to these agents via multiple optical modes, giving each analyte a distinct optical signature. Single-walled carbon nanotubes are environmentally sensitive and emit tissue-transparent near-infrared photoluminescence. By their encapsulation in short strands of synthetic DNA, we introduce a selective handle for changing their emission, allowing detection of DNA-damaging oxygen species or alkylating agents, by red-shifts in emission energy as well as optical quenching, giving multiple detection modes which result in analyte specificity. The nanotube-DNA complexes exhibit uptake into mammalian cells via endocytosis without cytotoxic effects and transduce analyte activity information live and in situ.