In vitro and in vivo mapping of drug release after laser ablation thermal therapy with doxorubicin-loaded hollow gold nanoshells using fluorescence and photoacoustic imaging

Abstract

Doxorubicin-loaded hollow nanoshells (Dox@PEG-HAuNS) increases the efficacy of photothermal ablation (PTA) by not only mediating efficient PTA but also through chemotherapy, and therefore have potential utility for local anticancer therapy. However, in vivo real-time monitoring of Dox release and temperature achieved during the laser ablation technique has not been previously demonstrated before. In this study, we used fluorescence optical imaging to map the release of Dox from Dox@PEG-HAuNS and photoacoustic imaging to monitor the tumor temperature achieved during near-infrared laser–induced photothermal heating in vitro and in vivo. In vitro, treatment with a 3-W laser was sufficient to initiate the release of Dox from Dox@PEG-HAuNS (1:3:1 wt/wt, 1.32×1012 particles/mL). Laser powers of 3 and 6 W achieved ablative temperatures of more than 50 °C. In 4T1 tumor–bearing nude mice that received intratumoral or intravenous injections of Dox@PEG-HAuNS, fluorescence optical imaging (emission wavelength = 600 nm, excitation wavelength = 500 nm) revealed that the fluorescence intensity in surface laser–treated tumors 24 h after treatment was significantly higher than that in untreated tumors (p=0.015 for intratumoral, p=0.008 for intravenous). Similar results were obtained using an interstitial laser to irradiate tumors following the intravenous injection of Dox@PEG-HAuNS (p=0.002 at t=24h). Photoacoustic imaging (acquisition wavelength = 800 nm) revealed that laser treatment caused a substantial increase in tumor temperature, from 37 °C to ablative temperatures of more than 50 °C. Ex vivo analysis revealed that the fluorescence intensity of laser-treated tumors was twice as high as that of untreated tumors (p=0.009). Histological analysis confirmed that intratumoral injection of Dox@PEG-HAuNS and laser treatment caused significantly more tumor necrosis compared to tumors that were not treated with laser (p<0.001). On the basis of these findings, we conclude that fluorescence optical imaging and photoacoustic imaging are promising approaches to assessing Dox release and monitoring temperature, respectively, after Dox@PEG-HAuNS–mediated thermal ablation therapy.

Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy

“…At high concentrations of DOX within HMs, the fluorescence signal of DOX is quenched; upon release through the shells, its fluorescence intensity increases significantly [39,40]. In the absence of a stimulus by HFMF, the local fluorescence intensity of DOX in the skin that received Lipos-HMs remained constant for a period of 24 h, suggesting that the diffusion of DOX through the PLGA shells of the HMs was rather slow.…”

Photoacoustic- and Magnetic Resonance-Guided Photothermal Therapy and Tumor Vasculature Visualization Using Theranostic Magnetic Gold Nanoshells

“…The PA phantom was constructed as previously described. 24 In brief, a plastic tube was filled with SPIO@AuNS (optical density 5), tube ends were sealed with epoxy, and the tube was suspended in a water-filled plastic tub. The water bath containing the phantom was heated from 21 C to 70 C, and the phantom was imaged at a laser wavelength of 808 nm.…”

Antitumor Therapy Using Nanomaterial-Mediated Thermolysis

“…After only one treatment, treated tumors were ablated and the mice remained tumor free for more than 90 days. Au nanoshells with dual PPT and drug release abilities were developed by Lee et al 121 In their study, Doxorubicin (DOX) loaded hollow Au nanoshells were treated to 4T1 tumor-bearing mice. Via fluorescence optical imaging and photoacoustic imaging, simultaneous DOX release and tumor temperature was monitored in real time.…”