Perfluorocarbon-Loaded Hollow Bi2Se3Nanoparticles for Timely Supply of Oxygen under Near-Infrared Light to Enhance the Radiotherapy of Cancer – ScienceOpen
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Abstract
Hollow Bi2 Se3 nanoparticles prepared by a cation exchange method are loaded with
perfluorocarbon as an oxygen carrier. With these nanoparticles, a promising concept
is demonstrated to enhance radiotherapy by not only using their X-ray-absorbing ability
to locally concentrate radiation energy in the tumor, but also employing near-infrared
light to trigger burst release of oxygen from the nanoparticles to overcome hypoxia-associated
radio-resistance.
The early detection of cancer can significantly reduce cancer mortality and saves lives. Thus, a great deal of effort has been devoted to the exploration of new technologies to detect early signs of the disease. Cancer biomarkers cover a broad range of biochemical entities, such as nucleic acids, proteins, sugars, small metabolites, and cytogenetic and cytokinetic parameters, as well as entire tumour cells found in the body fluid. They can be used for risk assessment, diagnosis, prognosis, and for the prediction of treatment efficacy and toxicity and recurrence. In this review, we provide an overview of recent advances in cancer biomarker detection. Several representative examples using different approaches for each biomarker have been reviewed, and all these cases demonstrate that the multidisciplinary technology-based cancer diagnostics are becoming an increasingly relevant alternative to traditional techniques. In addition, we also discuss the unsolved problems and future challenges in the evaluation of cancer biomarkers. Clearly, solving these hurdles requires great effort and collaboration from different communities of chemists, physicists, biologists, clinicians, material-scientists, and engineering and technical researchers. A successful outcome will result in the realization of point-of-care diagnosis and individualized treatment of cancers by non-invasive and convenient tests in the future.
Insufficient oxygenation (hypoxia), acidic pH (acidosis), and elevated levels of reactive oxygen species (ROS), such as H2O2, are characteristic abnormalities of the tumor microenvironment (TME). These abnormalities promote tumor aggressiveness, metastasis, and resistance to therapies. To date, there is no treatment available for comprehensive modulation of the TME. Approaches so far have been limited to regulating hypoxia, acidosis, or ROS individually, without accounting for their interdependent effects on tumor progression and response to treatments. Hence we have engineered multifunctional and colloidally stable bioinorganic nanoparticles composed of polyelectrolyte-albumin complex and MnO2 nanoparticles (A-MnO2 NPs) and utilized the reactivity of MnO2 toward peroxides for regulation of the TME with simultaneous oxygen generation and pH increase. In vitro studies showed that these NPs can generate oxygen by reacting with H2O2 produced by cancer cells under hypoxic conditions. A-MnO2 NPs simultaneously increased tumor oxygenation by 45% while increasing tumor pH from pH 6.7 to pH 7.2 by reacting with endogenous H2O2 produced within the tumor in a murine breast tumor model. Intratumoral treatment with NPs also led to the downregulation of two major regulators in tumor progression and aggressiveness, that is, hypoxia-inducible factor-1 alpha and vascular endothelial growth factor in the tumor. Combination treatment of the tumors with NPs and ionizing radiation significantly inhibited breast tumor growth, increased DNA double strand breaks and cancer cell death as compared to radiation therapy alone. These results suggest great potential of A-MnO2 NPs for modulation of the TME and enhancement of radiation response in the treatment of cancer.
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