| Summary: | 碩士 === 國立清華大學 === 生醫工程與環境科學系 === 104 === Non-invasive treatment possessing the property of relatively safe, low side effect and rapid recovery has been increasingly advocated. However, many current treatments such as deep brain stimulus or tumor treatment are still difficult to achieve this goal because they suffer from the insufficient delivery of therapeutic molecules and weak energy transfer at the targeted site. In this thesis, therefore, the non-invasive therapy integrated local energy transfer, therapeutic agents, targeting and chemotherapy into a functional carrier was designed and fabricated. To meet these goals, the porous silica/carbon nanosheets (PSC) supported lipid bilayers with biocompatibility that doubles as a conducting and high cargo payload platforms were developed. The functional lipids (1,2-dioleoyl–sn-glycero-3-phosphocholine,DOPC+1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) coated on PSC (lipo-PSC) through lipid fusion not only improve the cell viability but also enhance the cell uptake. Furthermore, once applying high-frequency magnetic field (HFMF) to PSC, the electromagnetic induction is performed on the electrical conductor, i.e., PSC, through the production of an electromotive force or voltage across, which is also known as Oersted’s law and Lenz's law.
In our first project, the lipo-PSC encapsulating nerve growth factor (NGF) was developed to enhance neural-like cell (PC12) differentiation. During HFMF stimulus, the lipo-PSC as electroactive NGF-releasing electrodes that stimulate the differentiation of PC12 cells through the combination of electrically stimulated cellular differentiation and electrically controlled NGF release. Once electrical treatment is applied, NGF release and electrically enhanced cellular differentiation lead to an obvious increase both in the percentage of cells with neurites and in the neurite length. In the result, the neurite length of cells can reach nearly 90 µm within 2 days. The average neurite length is significantly increased (four-fold) compared with untreated group. The electromagnetic activate lipo-PSC may be used as potential protein carriers for neural regeneration and neural prosthetics in tissue engineering applications.
In the second project, by encapsulating both hydrophilic and hydrophobic drugs, Doxorubicin (Dox) and Docetaxel (DTX), cocktail therapy of PSC was achieved synergistic therapeutic effects. Further conjugating targeting protein, Erbitux, on lipo-PSC leads to significantly enhanced cancer cell uptake of nanocarriers. Intracellular drug release triggered by external HFMF has also been achieved to kill cancer cells efficiently. Furthermore, a combination of therapeutic agents (DOX and DTX) delivered by the transcytosis of lipo-PSC into tumors was released through electromagnetic induction and successfully suppressed xenograft tumors in 16 days without distal harm. This sophisticated lipo-PSC is an excellent delivery platform for electromagnetic-responsive, and combined cocktail chemotherapy to facilitate tumor treatment and for use in other biological applications.
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