Phototherapy using immunologically modified carbon nanotubes to potentiate checkpoint blockade for metastatic breast cancer.

Metastasis is the major cause of cancer-death. Checkpoint inhibition shows great promise as an immunotherapeutic treatment for cancer patients. However, most currently available checkpoint inhibitors have low response rates. To augment the antitumor efficacy of checkpoint inhibitors, such as CTLA-4 antibodies, a single-walled carbon nanotube (SWNT) modified by a novel immunoadjuvant, glycated chitosan (GC), was used for the treatment of metastatic mammary tumors in mice. We treated the primary tumors by intratumoral administration of SWNT-GC, followed with irradiation with a 1064-nm laser to achieve local ablation through photothermal therapy (PTT). The treatment induced a systemic antitumor immunity which inhibited lung metastasis and prolonged the animal survival time of treated. Combining SWNT-GC-laser treatment with anti-CTLA-4 produced synergistic immunomodulatory effects and further extended the survival time of the treated mice. The results showed that the special combination, PTT + SWNT-GC + anti-CTLA, could effectively suppress primary tumors and inhibit metastases, providing a new treatment strategy for metastatic cancers.

Monitoring tissue temperature during photothermal therapy for cancer.

Phototherapies offer promising alternatives to traditional cancer therapies. Phototherapies mainly rely on manipulation of target tissue through photothermal, photochemical, or photomechanical interactions. Combining phototherapy with immunotherapy has the benefit of eliciting a systemic immune response. Specifically, photothermal therapy (PTT) has been shown to induce apoptosis and necrosis in cancer cells, releasing tumor associated antigenic peptides while sparing healthy host cells, through temperature increase in targeted tissue. However, the tissue temperature must be monitored and controlled to minimize adverse thermal effects on normal tissue and to avoid the destruction of tumor-specific antigens, in order to achieve the desired therapeutic effects of PTT. Techniques for monitoring PTT have evolved from post-treatment quantification methods like enzyme linked immunosorbent assay, western blot analysis, and flow cytometry to modern methods capable of real-time monitoring, such as magnetic resonance thermometry, computed tomography, and photoacoustic imaging. Monitoring methods are largely chosen based on the type of light delivery to the target tissue. Interstitial methods of thermometry, such as thermocouples and fiber-optic sensors, are able to monitor temperature of the local tumor environment. However, these methods can be challenging if the phototherapy itself is interstitially administered. Increasingly, non-invasive therapies call for non-invasive monitoring, which can be achieved through magnetic resonance thermometry, computed tomography, and photoacoustic imaging techniques. The purpose of this review is to introduce the feasible methods used to monitor tissue temperature during PTT. The descriptions of different techniques and the measurement examples can help the researchers and practitioners when using therapeutic PTT.

Nanotechnology-based photoimmunological therapies for cancer.

Phototherapy is a non-invasive or minimally invasive therapeutic strategy. Immunotherapy uses different immunological approaches, such as antibodies, vaccines, immunoadjuvants, and cytokines to stimulate the host immune system to fight against diseases. In cancer treatment, phototherapy not only destroys tumor cells, but also induces immunogenic tumor cell death to initiate a systemic anti-tumor immune response. When combined with immunotherapy, the effectiveness of phototherapy can be enhanced. Because of their special physical, chemical, and sometimes immunological properties, nanomaterials have also been used to enhance phototherapy. In this article, we review the recent progress in nanotechnology-based phototherapy, including nano-photothermal therapy, nano-photochemical therapy, and nano-photoimmunological therapy in cancer treatment. Specifically, we focus on the immunological responses induced by nano-phototherapies.

Determination of temperature distribution in tissue for interstitial cancer photothermal therapy.

BACKGROUND: Temperature increase in tumour tissue during photothermal therapy (PTT) is a significant factor in determining the outcomes of the treatment. Therefore, controlling and optimising temperature distribution in target tissue is crucial for PTT. In this study, we developed a unique ex vivo device to study the temperature distribution during PTT to be used as a guide for the desired photothermal effects for cancer treatment. METHODS: Bovine liver tissue buried inside agarose gel served as a phantom tumour surrounded by normal tissue. A thermostatic incubator was used to simulate tissue environment in live animals. The temperature distributions were measured by thermocouples with needle probes at different locations inside the target tissue, during laser irradiation using an 805-nm laser. RESULTS: The results obtained using the ex vivo device were verified by comparing the tissue temperature directly measured in animal tumours irradiated under the same conditions. With this model, the spatial distribution of temperature in target tissue can be monitored in real time. A two-dimensional temperature distribution in target tissue allows us to establish the correlations among laser parameters, temperature distribution and tumour size. In addition, the optimal temperature range for tumour destruction and immunological stimulation was determined using metastatic rat mammary tumour model. CONCLUSION: The device and method developed in this study can provide guidance for choosing the appropriate treatment parameters for optimal photothermal effects, particularly when combined with immunotherapy, for cancer treatment.