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The Challenge
In solid tumours the development of hypoxia leads to enhanced tumour survival and decreased efficacy of cancer treatments such as radiotherapy, some forms of chemotherapy and emerging sensitiser-based approaches that depend on oxygen for maximum efficacy.
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Addressing tumour hypoxia remains a clinical unmet need.
The Solution
Coated in a pH sensitive polymer, StimOxyGen is a nanoparticle formulation that dissolves at low pH and transiently generates oxygen in hypoxic tumours, thereby addressing one of the major bottlenecks to successful treatment of solid tumours.
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StimOxyGen has the ability to carry additional therapeutic payloads on the polymer coating. We have exploited this aspect to include a sensitiser to enhance the effects of photodynamic therapy (PDT) and sonodynamic therapy (SDT).
What is Hypoxia?
Hypoxia is defined as a lack of oxygen within tissues.
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In oncology, hypoxia is a common characteristic within solid tumours and leads to therapy resistance and poor patient outcomes.
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Hypoxia manipulates the tumour microenvironment at the cellular level by influencing processes such as:
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metastasis
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immune suppression
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angiogenesis
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cell proliferation and cell death
Photodynamic Therapy (PDT)
PDT is a novel anti-cancer treatment that requires 3 components:
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Photosensitiser (The sensitising drug)
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Light ( The stimulus)
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Molecular Oxygen
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The combination of sensitiser and ultrasound, in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS) and causes cell death via oxidative stress.
As oxygen is a key requirement for the generation of ROS in PDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using PDT can be a challenge, however this can be solved with StimOxyGen.
Sonodynamic Therapy (SDT)
SDT is an emerging anti-cancer treatment that requires 3 components:
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Sonosensitiser (The sensitising drug)
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Ultrasound ( The stimulus)
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Molecular Oxygen
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The combination of sensitiser and ultrasound, in the presence of molecular oxygen, generates cytotoxic reactive oxygen species (ROS) and causes cell death via oxidative stress.
As oxygen is a key requirement for the generation of ROS in SDT and given the fact that hypoxia is a characteristic of most solid cancerous tumours, treating hypoxic tumours using SDT can be a challenge, however this can be solved with StimOxyGen.
What can StimOxyGen do?
StimOxyGen has shown that it can generate enhanced levels of oxygen in an acidic environment
Oxygen generation with StimOxyGen is dose-responsive
StimOxyGen can temporarily increase in situ oxygen partial pressures from 0 mmHg up to 50 mmHg within 4 minutes post-administration
StimOxyGen can harbour an additional payload such as a sensitiser for SDT and achieve significant tumour growth delay in a human xenograft model of pancreatic cancer.
StimOxyGen can generate a dramatic SDT-mediated abscopal effect in a bilateral, syngeneic murine pancreatic tumour model.
This suggests that the StimOxyGen enhanced approach can be exploited to control metastatic disease.
