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Applications of Monocomponent Nanomaterials in Cancer Diagnosis and Autophagy-Mediated Therapy

Author: ZhangLi
Tutor: WenLongPing
School: University of Science and Technology of China
Course: Cell Biology
Keywords: nanocrystals manganese(Ⅱ) oxide fullerene derivate C60(Nd) magneticresonance imaging (MRI) autophagy p53 Doxorubicin (Dox) cancer diagnosis andtherapy
CLC: R73-3
Type: PhD thesis
Year: 2013
Downloads: 278
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Abstract


Despite remarkable advances in modern medical sciences, cancer remains a disease difficult to treat and keeps a leading cause of death worldwide. The enhanced permeability and retention (EPR) effects of a variety of organic and inorganic nanomaterials with well-controlled size, shape, charge can be exploited to achieve passive targeting of tumors for imaging and therapy. Novel multifunctional nanomaterials are recently emerging as promising tools for cancer diagnostic and therapeutic applications due to their unique characteristics. Most recent progress has focused on the fabrication of multicomponent nanocomposites to achieve magnetic resonance-targeted drug delivery, and magnetic nanomaterials can be facilely combined with mesoporous silica, noble metals, carbon, and fluorescent moieties. However, the multicomponents might induce antagonism to perform both magnetic resonance imaging (MRI) and chemotherapy at low efficiency in comparison with pure components. Therefore, it is highly desirable to find a novel and monocomponent multifunctional magnetic nanomaterial that can play a critical role in cancer therapy, while maintaining good properties in MR imaging (MRI). Fortunately, the integration of nanotechnology with molecular cancer biology and medicine has resulted in active developments of a novel emerging research area, nanobiotechnology, which can definitely make monocomponent nanoparticles the excellent theragnostic agents.Autophagy, which is an evolutionarily conserved and highly regulated dynamic intracellular process and cell-protective mechanism in mammalian cells for degrading long-lived proteins and defective organelles, has attracted much attention for the crucial role in physiology and pathology. In general, constitutively-active basal level of autophagy is known to be involved in the development, differentiation, and homeostasis in various organisms. Paradoxically, autophagy also leads to cell damage and human diseases, such as neurodegeneration and tumorigenesis. In recent years, the idea that various nanoparticles may induce autophagy in cancer cells has attracted increasing attention as it could be a useful new approach to treat cancer. In this dissertation, we represent some systematic research on autophagy induction and autophagy-mediated cancer chemotherapy elicited by two kinds of monocomponent nano-sized materials:Manganese(Ⅱ) oxide (MnO) nanocrystal and water-dispersed fullerene derivate C60(Nd).In part I, we report a kind of novel monocomponent hydrophilic and paramagnetic manganese(Ⅱ) oxide nanocrystal is prepared in polar solution by a one-pot microwave-assisted synthesis. This kind of nanocrystal can be taken up efficiently by cancer cells to serve as an excellent T1MRI contrast agent. Furthermore, we present multiple lines of convincing evidence to prove that MnO nanocrystals (NCs) elicit p53-activation independent and authentic functional autophagy via inducing autophagosome formation. Moreover, we maintain that the autophgy-inducing effects offer an indication for cancer therapy that MnO NCs combined with doxorubicin at a nontoxic concentration can have a definite synergistic effect on killing cancer cells in vitro and in vivo. In summary, we offer a integrated platform for cancer diagnosis and therapy simultaneously, which means "see and treat".In part Ⅱ, we show that water-dispersed C60(Nd), has greater potential in inducing autophagy and sensitizing chemotherapeutic killing of both common and drug-resistant cancer cells in a autophagy-dependent manner. Our results may ultimately lead to novel therapeutic strategies in cancer chemotherapy.

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