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العنوان
Study of the preparation and applications of nanoparticles as effective photosensitizers for photodynamic therapy testified in Caenorhabditis elegans model /
المؤلف
Mohamed, Shereen Mohamed Elsherbiny.
هيئة الاعداد
باحث / شيرين محمد الشربينى محمد
مشرف / تشينغ هوانغ
مشرف / تشينغ هوانغ
مشرف / تشينغ هوانغ
الموضوع
Photochemotherapy. Photodynamic therapy. Nanoparticles. Carbon quantum dots.
تاريخ النشر
2024.
عدد الصفحات
online resource (143 pages) :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الفيزياء وعلم الفلك
تاريخ الإجازة
1/1/2024
مكان الإجازة
جامعة المنصورة - كلية العلوم - قسم الفيزياء
الفهرس
Only 14 pages are availabe for public view

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Abstract

”Study of the preparation and applications of nanoparticles as effective photosensitizers for photodynamic therapy testified in Caenorhabditis elegans model Significant effort has been spent on developing effective cancer treatment methods (surgical, radiotherapy, chemotherapy, and phototherapy) owing to the high death rate caused by malignant tumors. Among these methods, the photodynamic therapy (PDT), as a burgeoning cancer treatment modality, has gained a lot of interest because of its non-invasive property, no drug resistance, and minimal side effect. Moreover, the PDT effect depends on the photosensitizer (PS) which is activated by light with an appropriate wavelength to generate reactive oxygen species (ROS), especially singlet oxygen (1O2), that can kill the cancer cells. Conventional photosensitizers (PSs) have some disadvantages such as low water-solubility, complex synthetic procedures, limited light penetration, low singlet oxygen quantum yield (1O2), and potentially high bio-toxicity, the clinical application of PDT is still limited. Therefore, the development of new photosensitizer agents is necessary for promoting the clinical application of PDT. Also, a high-throughput and rapid biological model to evaluate the PDT efficiency of these materials is required. Accordingly, we have carried out the relevant research and obtained the following results: Firstly, we prepared a carbon quantum dots (CQDs) based photosensitizer and investigated its corresponding PDT effects in Caenorhabditis elegans (C. elegans). The CQDs was prepared from broccoli as a natural raw material through a green synthesis method. The as-prepared broccoli-derived CQDs (BCQDs) showed excellent water solubility and optical properties, and it could generate 1O2 effectively under irradiated light with a wavelength of 660 nm with a high quantum yield (0.42). In the experiment for validating the PDT effect of BCQDs in C. elegans, the results revealed that the PDT efficiency of the BCQDs was dependent on the induction of germline apoptosis through the cep-1/p53 pathway. Further investigation confirmed the DNA damage of the worm by the BCQDs after sufficient light irradiation, which was testified by measuring the C. elegans mutants that have a loss of function in the genes involved in DNA damage response. This work has not only provided a new photodynamic agent but also introduced C. elegans as an easy model for rapid evaluation of the efficiency of PDT. Secondly, we prepared Bi2MoO6/MoS2/AuNRs (BMO-MSA) nanocomposite and investigated its PDT effect and related mechanism. The results showed the nanocomposite BMO-MSA possesses both high photodynamic ability and POD-like activity under NIR-II light irradiation. The as-prepared BMO-MSA nanocomposite not only generates effective 1O2 with quantum yield (0.32) upon 1064 nm illumination but also can produce .OH radical for CDT. Furthermore, the results demonstrated that the BMO-MSA nanocomposite has outstanding photothermal stability and photothermal conversion efficiency (30.23%). The in vivo experiments confirmed that it could induce the germline apoptosis of C. elegans via the cep-1/p53 pathway after being illuminated by light with a wavelength of 1064 nm. Further, investigations revealed its ability for the induction of DNA damage in the worms using the mutants that have a loss of function in the genes involved in DNA damage response. This work has not only provided a novel PDT agent which could be used for PDT in the NIR-II region but also demonstrated a new approach taking advantage of both PDT and CDT effects. As such, this Ph.D. thesis work not only provides new effective materials for PDT but also introduces C. elegans as an easy and effective model for PDT research.