Dissertation > Medicine, health > Basic Medical > Medical science in general > Biomedical Engineering > General issues > Biomaterial

The Role of Nanomaterials in Cancer Therapy

Author YangZuoZuo
Tutor WenLongPing
School University of Science and Technology of China
Course Cell Biology
Keywords Chemotherapy Nano -C60 Autophagy Light enhancement Radicals Dendrimers molecules Polyamide - amine Cancer Targeting Solubility 2D NMR technique Isothermal Titration heat
CLC R318.08
Type PhD thesis
Year 2008
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The first part of photocatalytic nano-fullerene due autophagy and adjuvant chemotherapy drugs to treat cancer research PART I Nano-C60 Sensitizes Chemotherapeutic Killing OfCancer Cells Through Autophagy Modulation of cancer chemotherapy poor efficacy of one of the main reasons is a chemotherapy drug for tumor cell killing efficiency as well as easy to produce drug resistance of tumor cells. Autophagy is a lysosome-associated intracellular degradation process, this process in evolution is conservative, and affects the response of tumor cells to chemotherapy. Has been proved that fullerene C60 can generate static autophagy characteristics, but so far people have not specific for this process. In the first part, we found that the fullerene C60 stably dispersed in water, nano-C60 crystal can cause abnormal cell autophagy. This along with increased autophagy and the autophagy cycle to reduce abnormal autophagy, has been enhanced by light stimulation, and the reaction is dependent on free radicals. Nano-C60 can cause autophagic cell dose does not cause cell death, but can enhance chemotherapy drugs to kill cancer cells (including drug-resistant cancer cells) effect, Atg5 autophagy genes must participate in this process. Our results for the first time proposed nano-C60 by regulating autophagy process to improve the efficacy of chemotherapy drugs reduce cancer cell resistance of this new biological functions, suggesting that nano-C60 has become a chemotherapy drug adjuvant potential application value. The the second portion polyamide - amine Dendrimers molecules in cancer targeting and drug carrier PART II Applications Of Poly (amidoamine) Dendrimers the of As CancerTargeting Device and Drug Carriers polyamide - amine (PAMAM) Dendrimers molecules having a tree structure of the artificial synthetic macromolecules. Such molecules having a large number of surface functional groups, a relatively hydrophobic internal cavity, the unique spherical geometry appearance, controlled size and molecular weight, and excellent dispersibility. Star-burst the branches-shaped molecules is becoming an excellent carrier for targeted drug delivery platform. In this part of the paper, we mainly study the cancer targeting drug carrier of PAMAM Dendrimers molecules in the PAMAM Dendrimers molecules and drug interactions. This part of the paper is divided into four chapters. Chapter Overview branches shaped molecules and their applications in the biomedical, especially for PAMAM Dendrimers molecules. The second Chapter synthetic cancer targeting vector-based of PAMAM Dendrimers molecules and biotin. And by flow cytometry and laser confocal microscopes and other technology to explore the targeting ability of the polymer at the cellular level and the targeting mechanism. Found that such branch-shaped molecule with biotin-based polymer carrier having a good targeting ability, such targeting effect in a dose-dependent and the dependence of the incubation time, energy-dependent, highly selective, and can be Specific inhibition of biotin. Such polymer carrier has superior biological compatibility, can be used as a potential nanocarrier platform used in clinical diagnosis and treatment. The third chapter we report the the PAMAM dendrimers molecule load anti-leukemia drug 6 - mercaptopurine Encapsulation efficiency. Conventional chemical therapy typically face a problem is the low water solubility of such a cytotoxic agent. Macromolecular carrier system can be used to increase the solubility of these drugs. The spherical polymer macromolecules which is highly branched molecules called dendrimers carrier from which come to the fore. Our study found that to PAMAM Dendrimers molecules of the amino-terminal wrapped insoluble anti-leukemia drug 6 - mercaptopurine and increase its water-soluble. Under alkaline conditions (pH 10), the wrapped highest efficiency of the drug, however, under acidic conditions, the drug Encapsulation efficiency decreased; salt concentration on Encapsulation efficiency had no effect. The fourth chapter of the the PAMAM dendrimers molecular interactions with non-steroidal anti-inflammatory drugs phenylbutazone. The solubility results show that the the PAMAM Dendrimers macromolecules greatly improved of Bute a solubility in water, and solubilization by the great influence of the concentration of the dendrimer, algebra, surface functional groups, as well as the pH value. 2D NOE spectra clearly show that phenylbutazone protons and third generation as well as the sixth generation dendrimers lumen proton NOE effect interactions produce many kinds of cross peaks. Solubility, two-dimensional NOE and isothermal titration calorimetry analysis results show that, parcels and electrostatic interaction common cause increased solubility of phenylbutazone. 2D NMR and isothermal titration calorimetry technology research Dendrimer its interaction between the guest molecules wrapped very useful tool.

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