<p>Fractionated photothermal therapy in a murine tumor model: comparison with single dose</p>

Abstract

Purpose: Photothermal therapy (PTT) exploits the light-absorbing properties of nanomaterials such as silica-gold nanoshells (NS) to inflict tumor death through local hyperthermia. However, in in vivo studies of PTT, the heat distribution is often found to be heterogeneous throughout the tumor volume, which leaves parts of the tumor untreated and impairs the overall treatment outcome. As this challenges PTT as a one-dose therapy, this study here investigates if giving the treatment repeatedly, ie, fractionated PTT, increases the efficacy in mice bearing subcutaneous tumors. Methods: The NS heating properties were first optimized in vitro and in vivo. Two fractionated PTT protocols, consisting of two and four laser treatments, respectively, were developed and applied in a murine subcutaneous colorectal tumor model. The efficacy of the two fractionated protocols was evaluated both by longitudinal monitoring of tumor growth and, at an early time point, by positron emission tomography (PET) imaging of 18 F-labeled glucose analog 18 F-FDG. Results: Overall, there were no significant differences in tumor growth and survival between groups of mice receiving single-dose PTT and fractionated PTT in our study. Nonetheless, some animals did experience inhibited tumor growth or even complete tumor disappearance due to fractionated PTT, and these animals also showed a significant decrease in tumor uptake of 18 F-FDG after therapy. Conclusion: This study only found an effect of giving PTT to tumors in fractions compared to a single-dose approach in a few animals. However, many factors can affect the outcome of PTT, and reliable tools for optimization of treatment protocol are needed. Despite the modest treatment effect, our results indicate that 18 F-FDG PET/CT imaging can be useful to guide the number of treatment sessions necessary.

Photothermal Therapy as Adjuvant to Surgery in an Orthotopic Mouse Model of Human Fibrosarcoma

“…Although PTT has been shown to have a significant treatment effect, many factors are involved in its success (e.g., tumor size, laser power, nanoparticle accumulation, etc. ), and it is often insufficient to achieve complete tumor removal [ 10 , 11 , 12 ]. As a result, studies applying PTT in combination with therapies such as immunotherapy and chemotherapy have recently yielded positive results.…”

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

“…One of the major problems with PTT is that heat distribution is often heterogeneous throughout the tumour, which leaves part of the tumour untreated. A new idea was proposed which uses silica gold nanoshells to deliver fractionated PTT [ 129 ]. Gold-based NPs are the main mediator of PTT because they offer biocompatibility, efficient light to hear conversion, ability to be tuned to absorb NIR light which penetrates tissue more deeply, a small diameter that enables tumour penetration, and simple gold thiol bioconjugation chemistry for the attachment of the desired molecule.…”

The use of a uPAR-targeted probe for photothermal cancer therapy prolongs survival in a xenograft mouse model of glioblastoma

“…For PTT, animals were anesthetized by breathing 4% sevoflurane, placed on the treatment platform and had the tumors irradiated for five minutes at a laser intensity of 2 W/cm 2 . The tumors were swabbed with glycerol, an index-matching agent, prior to the laser treatment to facilitate light penetration [35][36][37][38]. The temperatures reached on the tumor surface were recorded with a thermal camera, as described for the in vitro experiments.…”