depends on their NIR optical absorption for photoresponses, and their structure and surface properties leading to low cytotoxicity and efficient cellular uptake. An important challenge for photo-triggered nanocarriers lies in their cellular confinement within membrane-bound vacuoles. [9] This can limit therapeutic benefit by adversely modifying their optical properties due to agglomeration, [10] or reducing the efficacy of delivering therapeutic payloads by phototriggered drug release. [11,12] Recent studies have revealed that silicon nanowires with lengths of several micrometers can enter cells via nonendocytic pathways and demonstrate cytosolic distribution. [13] We hypothesized that NIR-active 1D nanomaterials with similar structural parameters might circumvent the drawbacks of vesicular confinement. Gold nanotubes (AuNTs) represent an intriguing subset of 1D nanomaterials. Their accessible inner cavity can in principle be loaded with drugs, [14,15] their open ends can be used as gates for controlled drug release, [16] and their lower heat capacity enables better pulse heating for photoacoustic imaging and photothermal therapy. [17] Despite the potential merits of AuNTs, their lack of NIR absorption and our limited understanding of cellular interactions have hindered their exploitation. For example, the pentagonal AuNTs synthesized by Bi and The generation of effective and safe nanoagents for biological applications requires their physicochemical characteristics to be tunable, and their cellular interactions to be well characterized. Here, the controlled synthesis is developed for preparing high-aspect ratio gold nanotubes (AuNTs) with tailorable wall thickness, microstructure, composition, and optical characteristics. The modulation of optical properties generates AuNTs with strong near infrared absorption. Surface modification enhances dispersibility of AuNTs in aqueous media and results in low cytotoxicity. The uptake and trafficking of these AuNTs by primary mesothelioma cells demonstrate their accumulation in a perinuclear distribution where they are confined initially in membrane-bound vesicles from which they ultimately escape to the cytosol. This represents the first study of the cellular interactions of high-aspect ratio 1D metal nanomaterials and will facilitate the rational design of plasmonic nanoconstructs as cytosolic nanoagents for potential diagnosis and therapeutic applications.
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