Abstract
As a model radio-photodynamic therapy (RPDT) agent, we developed a multicomponent nanomaterial by anchoring conjugated chromophores on the surface of scintillating chrysotile nanotubes. Its ultimate composition makes the system a scintillation-activated photosensitizer for the singlet oxygen production. This nanomaterial shows a remarkable ability to enhance the production of singlet oxygen in an aqueous environment, under X-ray irradiation, boosting its production by almost 1 order of magnitude. Its efficiency as a coadjutant for radiotherapy has been tested in vitro, showing a striking efficacy in enhancing both the prompt cytotoxicity of the ionizing radiation and the long-term cytotoxicity given by radiation-activated apoptosis. Notably, the beneficial activity of the RPDT agent is prominent at low levels of delivered doses comparable to the one employed in clinical treatments. This opens the possibility of effectively reducing the therapy exposure and consequently undesired collateral effects due to prolonged exposure of patients to high-energy radiation.
Highlights
The energy transfer from the nanoscintillator promotes the first excited singlet state of the PS. This can recombine radiatively, producing fluorescence, or non-radiatively by intersystem crossing (ISC) toward its triplet state, from which a subsequent nonradiative energy transfer to the molecular oxygen dispersed in the cellular environment sensitizes the population of the cytotoxic singlet oxygen.[37]
The detailed analysis of intermolecular interactions on NT surfaces to shed light on these aspects would require further dedicated investigations, but, in general, these results show that the excited-state recombination dynamics of Erythrosine B (ErB) and Bengal Rose is heavily affected by their arrangement on the NT surface, with potential detrimental consequences on their efficacy as PSs
Recent research studies proved that radio-photodynamic therapy (RPDT) is efficient in the treatments of oncological diseases
Summary
Over the past few years, biomedical science has recognized the crucial role that nanotechnology can play in the field thanks to the development and use of nanoparticles in theranostics, which allows a deeper investigation of biological processes, faster diagnosis of diseases, accurate monitoring of specific injured tissues or organs, and, importantly, the improvement of some traditional therapeutic treatments.[1−5] Due to their benefits with respect to larger systems, such as a high surface-to-volume ratio; facile surface functionalization; and tailorable optical, magnetic, and structural properties crucial for the adaptability to satisfy specific targets, nanomaterials are ideal carriers for chemo- and phototherapeutic agents or radiosensitizers across several physiological barriers.[6,7] nowadays, a plethora of nanoscale materials, such as metallic and semiconductor nanoparticles, fluorites, and metal/lanthanide oxides, as well as organic and hybrid systems, are successfully exploited in advanced diagnostic and imaging techniques or innovative therapeutic approaches against cancer and other deadly diseases,[8−11] as demonstrated by the more and more increasing number of nanosystems approved by the Food and Drug Administration (FDA) agency.[8,12]In particular, biomedicine is moving toward the use of radioluminescent nanoparticles, that is, nanoscintillators, which are able to absorb and convert the ionizing radiation (X- or γrays) into a large number of UV/visible (UV/vis) photons exploitable to boost the efficacy of diagnosis routes, in nuclear medicine for preclinical mapping and intraoperative imaging and radiation dosimetry, and as coadjutants in oncological therapies.[13−16] The search for innovative therapies overtaking state-of-the-art oncological treatments is challenging. Conventional cancer treatment options chemotherapy, radiotherapy (RT), and surgery are still associated with systemic side effects, disease recurrence, and drug/radio resistance of malignant cells. Ionizing radiation is used in approximately 50% of all cancer treatments to stop the rapid proliferation of cancer cells directly by damaging their DNA and by thermal shock or indirectly by forming cytotoxic free radicals, that is, reactive oxygen species (ROS) such as hydroxyl radicals and singlet oxygen, upon interaction with the intracellular aqueous environment.[17,18] RT is limited by the maximum radiation dose that can be given to a tumor mass without incurring significant injuries to the adjacent tissues or organs.[19] In order to maximize the therapeutic
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