An Urchin-Shaped Copper-Based Metalloporphyrin Nanosystem as a Sonosensitizer for Sonodynamic Therapy

Sonodynamic therapy (SDT), as a novel cancer therapy strategy, might be a promising approach due to the depth-penetration property in tissue. Sonosensitizers are the key element for efficient SDT. However, the development of sonosensitizers with strong sonosensitization efficacy is still a significant challenge. Herein, an urchin-shaped copper-based metalloporphyrin liposome nanosystem (FA–L–CuPP) is constructed and identified as an excellent sonosensitizer. Under ultrasound (US) irradiation, FA–L–CuPP can be highly excited to generate several reactive oxygen species (ROS), such as singlet oxygen (1O2) and free radicals (⋅OH). The molecular orbital distribution calculations reveal that a strong intramolecular charge transfer might occur in the CuPP complex under US irradiation, which could afford enough energy to the surrounding O2 and H2O to concert 1O2, O2− and ⋅OH. Working as “ammunitions”, the largely produced ROS can kill 4T1 tumor cells, effectively inhibiting tumor growth. This work provides an urchin-shaped nanosonosensitizer based on a copper complex, which might provide an idea to design a novel sonosensitizer for noninvasive and precise SDT antitumor applications.

Review of therapies using TiO2 nanomaterials for increased anticancer capability

Recently, Titanium dioxide (TiO2) has been studied as an alternative to treat cancer diseases under different activation therapies. The aim of this review was to describe the effect of TiO2 nanoparticles (NPs) on some cancer cell lines and their interaction with phototherapies such as photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and ultraviolet therapy (UV) for anticancer treatment. The use of TiO2 combined with PDT, PTT, SDT, or UV has shown a remarkable capacity to enhance the killing of cancer cells through reactive oxygen species formation. Thus, the combination of TiO2 and activation therapies exhibited great potential and could be a viable anticancer treatment strategy. However, more studies on phototherapies in combination with TiO2 and their effects at under different experimental conditions (TiO2 concentration, type of cancer cells, and intensity and frequency of therapies) are necessary to guarantee the safe use of this kind of therapy.

Current Landscape of Sonodynamic Therapy for Treating Cancer

Recent advancements have tangibly changed the cancer treatment landscape. However, curative therapy for this dreadful disease remains an unmet need. Sonodynamic therapy (SDT) is a minimally invasive anti-cancer therapy involving a chemical sonosensitizer and focused ultrasound. A high-intensity focused ultrasound (HIFU) beam is used to destroy or denature targeted cancer tissues. Some SDTs are based on unfocused ultrasound (US). In some SDTs, HIFU is combined with a drug, known as a chemical sonosensitizer, to amplify the drug’s ability to damage cancer cells preferentially. The mechanism by which US interferes with cancer cell function is further amplified by applying acoustic sensitizers. Combining multiple chemical sonosensitizers with US creates a substantial synergistic effect that could effectively disrupt tumorigenic growth, induce cell death, and elicit an immune response. Therefore, the minimally invasive SDT treatment is currently attracting attention. It can be combined with targeted therapy (double-targeting cancer therapy) and immunotherapy in the future and is expected to be a boon for treating previously incurable cancers. In this paper, we will consider the current state of this therapy and discuss parts of our research.

Metal-Based Nanomaterials Incorporate with Ultrasound as Acceptable Approach towards Cancer Therapy

Among current biological researches, there have a plenty of works related cancer therapy issues by using functional or pure-phased composites in non-invasive strategies. Especially in fabricating anticancer candidates, functional composites are divided into different sorts with different characteristics. Additionally, nanotechnology provides various approaches in utilizing composites’ functionality for cancer diagnostics and therapeutics. Compared with previous Photodynamic Therapy (PDT), Photo-Thermal Therapy (PTT), chemotherapy and radiotherapy, ultrasound is used to activate sonosensitizer to produce cytotoxic Reactive Oxygen Species (ROS) toward target cancer cells. In recent years, the form of Sonodynamic Therapy (SDT) has been making much effort to develop highly efficient metal based Nanomaterials (NMs) as sonosensitizers, which can efficiently generate ROS and has the advantages of deeper tissue penetration. However, the traditional sonosensitizers, such as porphyrins, hypericin, and curcumins suffer from complex synthesis, poor water solubility, and low tumor targeting efficacy. For contrasting this limitation, the metal based inorganic NMs show biocompatibility, controllable physicochemical properties, and ease of achieving multifunctional properties, which greatly expanded their application in SDT. In this review, we systematically summarize the metal based inorganic NMs as carrier of molecular sonosensitizers, and produce ROS under ultrasound. Moreover, the prospects of advanced metal based further materials application are also discussed.

P-P11 A tumour responsive, oxygen-generating nanoparticle to combat hypoxia in pancreatic tumours

Background Pancreatic cancer remains a significant therapeutic challenge and its poor prognosis has remained relatively unchanged for the past 40 years. Pancreatic tumours are highly desmoplastic and impenetrable lesions in which both gas and mass transfer is severely compromised. This leads to the development of hypoxia within the tumour and this compromises therapeutic approaches that rely on cytotoxic reactive oxygen species, e.g. photodynamic therapy, sonodynamic therapy and radiotherapy. Hypoxia also results in a relatively low pH within the tumour microenvironment. Here we describe a pH sensitive nanoparticle that can generate oxygen in the tumour and enhance ROS generating therapeutic approaches. Methods CaO2 NPs were generated by exposing to low frequency ultrasound and subsequently coated using a polymethacrylate polymer that becomes soluble at pH 6.4. For some studies, the sonosensitiser, Rose Bengal was attached to the particles. Oxygen generation in tumours (BxPC3) was demonstrated by inserting a dissolved oxygen probe into tumours following IV administration of particles. Particles were also employed together with photodynamic therapy (PDT) and sonodynamic therapy (SDT) using human xenograft and syngeneic pancreatic tumour models. In some cases, tumour tissues were recovered and analysed for tumour infiltrating immune cells using flow cytometry. Results Conclusions Coating CaO2 nanoparticles with a pH sensitive polymer provides in situ oxygen generation in tumours. Transient provision of oxygen enhances therapies that depend on the generation of cytotoxic reactive oxygen species. When used with SDT, and using a bilateral syngeneic pancreatic tumour model, a powerful abscopal effect was observed and this was shown to be immune-mediated. The above data suggest that the particles may be exploited to enhance other therapies that depend on the generation of ROS, e.g. radiotherapy, and further suggest that the approach can be used to treat either local or disseminated forms of pancreatic cancer.