A gold nanorod (GNR)-photosensitizer complex was developed for noninvasive near-infrared fluorescence imaging and cancer therapy. We showed that (a) fluorescence emission and singlet oxygen generation by AlPcS(4) were quenched after complex formation with GNRs; (b) 4-fold greater intracellular uptake and better in vitro phototoxicity were observed in GNR-AlPcS(4)-treated cells than in free AlPcS(4)-treated cells; and (c) after intravenous injection of the GNR-AlPcS(4) complex, tumor sites were clearly identified on near-infrared fluorescence images as early as 1 h after injection. The tumor-to-background ratio increased over time and was 3.7 at 24 h; tumor growth reduced by 79% with photodynamic therapy (PDT) alone and by 95% with dual photothermal therapy (PTT) and PDT. This novel multifunctional nanomedicine may be useful for near-infrared fluorescence imaging and PTT/PDT in various cancers.
We report on the development of photosensitizer-conjugated gold nanorods (MMP2P-GNR) in which photosensitizers were conjugated onto the surface of gold nanorods (GNR) via a protease-cleavable peptide linker. We hypothesized that fluorescence and phototoxicity of the conjugated photosensitizers would be suppressed in their native state, becoming activated only after cleavage by the target protease matrix metalloprotease-2 (MMP2). Quantitative analysis of the fluorescence and singlet oxygen generation (SOG) demonstrated that the MMP2P-GNR conjugate emitted fluorescence intensity corresponding to 0.4% ± 0.01% and an SOG efficiency of 0.89% ± 1.04% compared to free pyropheophorbide-a. From the in vitro cell studies using HT1080 cells that overexpress MMP2 and BT20 cells that lack MMP2, we observed that fluorescence and SOG was mediated by the presence or absence of MMP2 in these cell lines. This novel activatable photosensitizing system may be useful for protease-mediated fluorescence imaging and subsequent photodynamic therapy for various cancers.
The photothermal properties of gold nanorods (GNRs) provide an opportunity for the clinical application of highly efficient and tumor-specific photothermal therapy. For the effective hyperthermic ablation of tumor tissue using GNRs, it is essential to maintain a homogeneous therapeutic temperature in the target tissue during treatment. This study investigates whether the concentration of GNRs affects the distribution of the temperature increase during hyperthermal therapy. The investigation is conducted using polyacrylamide phantoms containing varying amounts of GNRs. In 0.1, 0.25, and 0.5 nM GNR-suspended phantoms, the change in temperature is relatively uniform along the depth of each phantom during laser irradiation at 2 W cm(-2) . In 1.0, 2.0, and 5.0 nM GNR-suspended phantoms, the rates of temperature increase in the deep regions of the phantoms decrease with increasing GNR concentration. At a laser irradiation of 5 W cm(-2) , the temperature of the GNR-suspended phantoms increases at a faster rate, whereas the range of GNR concentrations for maintaining the homogeneity of the temperature increase is not affected. This suggests that the concentration of GNRs is the major determinant of the depth-related temperature increase during hyperthermic ablation. Therefore, prior to the clinical application of hyperthermic ablation using GNRs, the concentration of GNRs has to be optimized to ensure a homogeneous distribution of therapeutic temperature in the targeted tissue.
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