Bright Alkyl Quantum Defects Govern Early Carbon Nanotube Pharmacokinetics in Mice

Fluorescent quantum defects in single-wall carbon nanotubes (SWCNTs) are a major advance in nanocarbon research, owing to their bright, single-photon emission at telecom wavelengths and versatile conjugation chemistries for biomedical sensing and disease targeting. Here, we introduce an efficient, oxygen-free sonochemical route that generates long-chain alkyl defects, simultaneously shortening nanotubes and producing a bright, homogeneously emissive (6,5) SWCNT ensemble. Among 15 screened reactants, the branched-chain NiaproofⓇ 4, which molecular dynamics simulations show packs more densely and uniformly than linear surfactants, yields a 3.4-fold brightness enhancement and a sharp emission peak near 1108 nm. Single-particle spectroscopy reveals J-aggregate emission redshifts at high defect densities, and fibrinogen titration shows defect chemistry governs protein-driven coating displacement. Using a home-built short-wave infrared imaging system (25 mW cm–2, 989 nm excitation, 1150 nm long-pass collection), we show that these sparse defects (∼9–16 μm–1) drive different pharmacokinetics between NiaproofⓇ 4– and lipid-PEG–functionalized (6,5) at early time points, converging as protein-corona formation masks the underlying chemistry. Histology localizes the nanotubes within macrophages of mononuclear phagocyte system–associated organs. Intravenous administration (∼41 μg kg–1) causes no acute toxicity and a short ∼2-day retention. The NiaproofⓇ 4 group exhibits a reduced circulating myeloid-cell fraction following corona formation, which may reflect organ recruitment and sequestration, while the accompanying increase in CD3+ T cells may partly reflect a proportional shift in leukocyte composition.