Photostability of Gold Nanorods upon Endosomal Confinement in Cultured Cells

Abstract

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.

Ready-to-use protein G-conjugated gold nanorods for biosensing and biomedical applications

“…Meanwhile, a micro BCA™ protein assay was implemented to assess the number of antibodies bound per particle, by the subtraction of unreacted antibodies during the amidation step. The fractions of antibodies left unreacted in the supernatant from the first and second cycle of centrifugation after covalent binding were (82 ± 10)% and below 1%, which amounts to an average of 40 ± 20 antibodies bound per particle, as calculated from the number of particles [ 66 ] and molecules of antibody dosed per mL. We note that this estimate is in reasonable agreement with previous reports on similar protocols for chemical binding of antibodies [ 62 ].…”

“…In turn, the concentration of AP was calibrated from a preliminary measurement of its optical absorbance vs. that of a standard solution of bovine serum albumin, upon compensation for their relative molecular weights. Knowledge of both the number of particles [ 66 ] and molecules of enzyme per mL conveys the number of events of molecular recognition per particle, under the assumption that each event of molecular recognition brings one molecule of enzyme, as is sketched in Fig. 1 .…”

Polylysine as a functional biopolymer to couple gold nanorods to tumor-tropic cells

“…A comparison between the optical spectra in Figs. 1 , 2 shows that, after being phagocytized, gold nanorods maintained most of their plasmonic features [ 56 , 72 ]. Some broadening and red-shift of both bands is ascribed to the effect of plasmonic coupling of nearby particles that occurs upon endosomal confinement [ 53 , 73 ].…”

Photostability of Contrast Agents for Photoacoustics: The Case of Gold Nanorods

“…Conversely, since the typical repetition rate is in the order of few Hz up to around a kHz in some cases, and thermalization with the environment takes less than about 1 ns, cumulative heating from pulse to pulse within the single particle is irrelevant. In some passages, it is also important to clarify that, with a thermal diffusivity in water in the order of 100 nm /ns [ 134 ], the typical length scale involved in PAI is in the order of few tens of nm, and so thermal coupling from particle to particle is often negligible as well [ 135 ]. As a consequence, it is only the fraction of particles in resonance with the optical trigger that are at risk of reshaping [ 136 ], as will be discussed in Section 4.3 .…”