The use of gold nanorods as contrast agents for the optical hyperthermia of cancer is receiving ever more attention. However, their selective delivery to tumors still remains an outstanding problem. In most cases, the identification of suitable molecular targets is complicated by the lack of qualitative differences between healthy and cancer cells. The focus of prior work has mainly been on the cancer cells per se. Instead, here, the aim is moved to secondary fingerprints that arise in response to the cancer microenvironment. One common feature of tumors is a combination of poor oxygenation and high oxygen consumption, which generates hypoxia. Hypoxic cells need to switch to an anaerobic metabolism, which is accompanied by a multitude of molecular processes, including the expression of transmembrane isoforms of carbonic anhydrases. Here, gold nanorods are conjugated with selective inhibitors of these enzymes, in order to recognize and hit hypoxic cells. The cellular uptake, cytostatic activity and capacity to impart an optical sensitization of these particles is shown to display a strong dependence on environmental oxygenation.

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Ref. [82] was not included in the originally published version of this article. It should be added to the second paragraph on page 7179, which then reads as follows: "More recently, the notion to exploit the natural tropism of cells, such as tumor-associated macrophages, [35][36][37][38][39] T cells, [40,82] mesenchymal stem cells, [41][42][43] and neural stem cells, [44,45] has begun to emerge as a radical alternative."Ref.

The photoinstability of plasmonic particles remains one remarkable obstacle before their clinical penetration as powerful contrast agents, for instance, in photoacoustic imaging. In particular, gold nanorods easily revert to nanospheres and so lose their best optical features under exposure to few-nanoseconds-long laser pulses. While this issue is attracting much attention and stimulating ad hoc solutions, such as the addition of rigid shells, the biological environment may cause even more instability. For instance, a frequent outcome of the interaction between this type of particles and malignant or immune cells is their tight confinement into endocytic vesicles. In this study, we assess whether this configuration may make an adverse impact on the photostability of gold nanorods, due to the effect of heat confinement. We compare experimental measurements from a limited set of representative samples and verify their relevance by the use of numerical simulations. Under conditions that are typical for photoacoustic microscopy, we estimate the threshold fluence for the onset of photoinstability to remain around 7 mJ•cm −2 , independent of the distance among neighboring particles, within accessible limits. Then, we simulate the effect of pulse duration in our model of endocytic confinement. Only in a μs regime of lesser potential for biomedical optics do we predict this configuration to destabilize the gold nanorods, still by as little as 15−20%. Our results span from the femtosecond up to the continuous wave regimes of irradiation and suggest that the biological interface does not pose a major threat on the photostability of plasmonic particles for most biomedical applications, including the photoacoustic imaging and photothermal ablation of cancer.