Nanoshell-mediated photothermal therapy improves survival in a murine glioma model

Abstract

We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica–gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male Icr-Tac:ICR-PrkdcSCID mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

Nanoshell-mediated photothermal therapy can enhance chemotherapy in inflammatory breast cancer cells

“…4 Subsequent exposure of the tumor to light at the nanoparticles' resonant wavelength causes synchronized oscillation of the nanoparticles' conduction-band electrons that results in the production of heat sufficient to damage the cancer cells. 2,5 To maximize the success of PTT, nanoparticles are designed to absorb near-infrared (NIR) wavelengths of light, which penetrate more deeply into tissue than other wavelengths. 6 Since heat is produced only where activating light and nanoparticles are both present, damage to healthy cells outside the tumor is minimal.…”

“…7,8 Thus, PTT is advantageous for cancer treatment because it is highly effective, minimally invasive, and offers limited side effects. Accordingly, there are several gold-based, NIRabsorbing nanoparticles being investigated for PTT, including silica core-gold shell nanoshells, 5,9,10 gold nanorods, 11 gold-gold sulfide nanoparticles, 12 hollow gold nanospheres, 13 and gold nanocages. 14 We selected nanoshells for use in our study, which demonstrates that low-dose PTT can sensitize cancer cells to chemotherapy by promoting drug accumulation in cells, because they are the furthest along in clinical development and are currently being evaluated in multiple clinical trials.…”

Nano Gold and Biomedicine: Scientific Letter

“…Ayrıca tümör hücrelerine hedeflenmesi ile hastalığın erken tanı ve teşhisine olanak sağla-makta, buna paralel olarak tümöral yayılımın optik, termal ya da termaoakustik görüntüleme teknikleri ile izlenmesini ve sonrasında fototermal olarak yok edilmesini de mümkün kılmaktadır. 55,56 Altın nanopartikülleri ile sadece belirli hücre hatlarına hedefleme yapılmayıp, aynı zamanda çe-kirdek, mitokondri, golgi aygıtı ve endoplazmik retikulum gibi özgül hücre içi organellere de hedefleme yapılmaktadır. [57][58][59] Özellikle gen taşıyıcısı olarak altın nanopartiküller ile çekirdeğe hedefleme yapılmakta ve bozuk genler tedavi edilmektedir.…”

Photothermal therapy of melanoma tumor using multiwalled carbon nanotubes

“…Internalized nanoparticles (NPs) to the tumor sites could be stimulated by laser irradiation, to produce localized heat in the range of 40°C-45°C so as to destroy cancer cells. [2][3][4][5] NPs such as single-walled carbon nanotubes, 6 multiwalled carbon nanotubes (MWNTs), 7,8 graphene, 9,10 iron oxide NPs, 11 gold nanorods, 12 and gold nanoshells 13,14 are used to transform NIR radiation to vibrational energy. Therefore, heat generation based on laser irritation could elevate malignant tissues' temperature and destroy tumors.…”