癌症是一種疾病，其特徵在於異常的細胞增生，且是由正常細胞的遺傳物質的損傷和/或突變引起的。癌症治療中，手術、放射治療和化療是最常使用的。在化療的情況下，控制藥物的釋放是最主要的挑戰之一。為了解決這個問題，設計和製造具反應性的奈米藥物載體並確保藥物到達患部並釋放。在使用不同的刺激如光，熱，pH變化，磁場，酶或氧化還原時，功能性材料透過物理或化學變化改變其性質，並按需求釋放載體。然而，在應答奈米藥物載體技術實現之前，需要充分研究和優化奈米藥物載體的參數，例如尺寸，藥物負載能力和由內部或外部刺激的變化引起的藥物動力學，以便減少化療的副作用，延長藥物釋放。在本論文中，合成了含有硒化物的聚合物應答奈米載體，確認其遞送抗癌藥物（阿黴素），並且已經用於增強化療對抗癌症效率。在第一項工作中，合成並確認了多應答（氧化還原，ROS和γ-輻射）硒化物連接的聚（乙二醇）奈米凝膠。拉曼光譜和X-射線光電子光譜分析證實了形成（聚乙二醇-硒）奈米凝膠，而掃瞄式電子顯微鏡和動態光散射儀顯示出均勻的球形奈米顆粒，平均直徑<200奈米。透過HeLa細胞測試合成材料的細胞毒性。透過透析法包住阿黴素，並透過透析法進行奈米凝膠硒化物應答GSH，H2O2和γ輻射藥物釋放。在第二項工作中，合成了氧化還原應答的雙（甲氧基聚（乙二醇））-聚（ε-己內酯）奈米粒子作為藥劑載體。氫譜、碳譜和傅立葉紅外光譜証明了三團聯共聚物的合成，透過奈米粒徑及介面電位量測儀測量奈米顆粒的粒徑和表面電位。使用FAM和多功能場發射掃描式電子顯微鏡研究奈米顆粒的形態。在正常細胞和癌細胞上測試進行細胞存活率分析證實合成的奈米顆粒的毒性較小。透過透析方法加載阿黴素，結果顯示該物質具有高包封效率。透過模擬GSH（6mM）和0.1％H2O2的細胞內水平來評估阿黴素釋放研究，藥物釋放曲線的結果表明奈米顆粒具敏感性。對還原劑和氧化劑有所應答。使用螢光成像研究負載阿黴素的奈米顆粒在癌症和正常細胞上的細胞攝取和細胞內藥物釋放。此外，使用3D腫瘤球體研究了負載阿黴素的奈米顆粒的定位和負載阿黴素的奈米顆粒的抗癌和抑制腫瘤生長。因此，含有雙（聚乙二醇-硒）-聚己內酯奈米顆粒的合成硒化物因其良好的生物相容性，選擇性藥物釋放到癌細胞中，對氧化還原高敏感性以及作為疏水性藥物的載體的是用於癌症治療的極有潛力的材料並提高癌症化療的效率。

Cancer is a disease that is characterized by uncontrolled cell growth and an absence of cell death and it is caused by damage and/or mutations in the genetic material of normal cells. Among different types of cancer treatments, surgery, radiotherapy, and chemotherapy are the most commonly used. In the case of chemotherapy, the controlled release of therapeutics has been one of the major challenges. To address this problem, the design and fabrication of stimuli-responsive nanomaterials are pursued to guarantee the controlled release of drug for a long period of time to the site of action. Upon applying different stimuli such as light, heat, pH change, magnetic field, enzymes or redox, functional materials change their physicochemical properties through physical changes or chemical reactions, allowing the release of loaded agents on demand. However, before the stimuli-responsive nanocarrier drug delivery technology becomes a reality, important parameters of the nanoparticles such as size, drug loading ability and sustained release kinetics due to the variation of internal or external stimuli need to be well studied and optimized in order to reduce the side effects of chemotherapeutic agents and prolong the drug releasing profile in a controlled manner. In this dissertation, multi-stimuli responsive nanocarriers based on diselenide linkage containing polymers were synthesized and characterized for the delivery of anticancer drug(Doxorubicin) which have been used to enhance the chemotherapeutic efficiency against cancers. In the first work, multi-stimuli (redox, ROS, and gamma-radiation) responsive diselenide linked poly(ethylene glycol) nanogels was synthesized and characterized. The Raman and XPS analysis confirmed the formation (PEG-SeSe)n nanogels while SEM and dynamic light scattering revealed uniform spherical nanoparticles with an average diameter of < 200 nm. The cytotoxicity of the synthesized material was tested using HeLa cells. Doxorubicin (DOX) was encapsulated via dialysis method and the drug release from diselenide containing nanogels in response to GSH, H2O2 and gamma radiation was conducted by dialysis method. In the second work, a redox-sensitive Bi(methoxyl Poly(ethylene glycol))-Poly(ε-caprolactone) nanoparticles were synthesized as a carrier of pharmaceutical agents(DOX).1H-NMR,13C-NMR and FTIR analysis confirmed the formation of Bi(mPEG-SeSe)-PCL triblock copolymer while the particle size and zeta potential of the nanoparticles were measured by DLS. The morphology of the nanoparticles was investigated using AFM and FE-SEM. The MTT assays tested on both normal and cancer cells confirmed less toxicity of the synthesized nanoparticles. DOX was loaded via dialysis method and the result showed the material has high encapsulation efficiency. DOX release study was evaluated by mimicking the intracellular level of GSH(6mM) and 0.1% H2O2, the results of the drug release profile indicated that the nanoparticles were sensitive to both reductant and oxidant stimuli. The cellular uptake and intracellular drug release of DOX-loaded nanoparticles were investigated on cancer and normal cells using fluorescence imaging. In addition, the localization of DOX-loaded nanoparticles and anticancer and tumor growth inhibition activity of DOX-loaded nanoparticles was studied using 3D-tumor spheroids. Thus, the synthesized diselenide containing Bi(mPEG-SeSe)-PCL nanoparticles are promising materials for cancer treatment because of its good biocompatibility, selectively drug release into cancer cells, high sensitivity towards redox environment and the possible usage as a carrier of the hydrophobic drug to enhance the efficiency of cancer chemotherapy.

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