表面自組裝修飾層為奈米材料提供方便且有效的界面功能，可微調表面物理化學性質、保持良好膠體懸浮性、可生物功能化與產生環境應變性。但是，常用的poly(ethylene glycol) (PEG)修飾材料在高溫與高鹽環境下，立即喪失水合能力，造成大量非特異性吸附與顆粒聚集，進而影響奈米粒子的應用。這些問題凸顯新一代奈米材料的表面改質技術的必要性，本計畫將開發生物啟發高穩定雙離子修飾物(bioinspired zwitterionic cysteine betaine, Cys-b)，並應用在中空金包銀奈米殼(hollow Ag@Au nanoshell)，提供創新標靶式光熱治療奈米系統，將近紅外光有效轉成熱，快速灼燒癌細胞。此超親水雙離子修飾物Cys-b提供奈米殼抵抗生物沾黏、高膠體穩定性與光熱穩定性。此研究基於不同的水合機制，PEG靠氫鍵與水分子作用，易受溫度影響，而雙離子材料藉由離子水合作用，高溫下仍然維持高水合。Cys-b藉由硫醇基與奈米殼進行自組裝表面修飾，快速形成緊密排列之奈米尺度薄膜。我們將在乳癌細胞為標的，進行光熱治療，驗證Cys-b與anti-HER2抗體修飾後之奈米殼的標靶治療功效。本計畫將規劃四大方向：1.Cys-b與奈米殼之合成與物理化學鑑定；2.建立標靶式光動治療乳癌細胞；3.響應式二維Cys-b結晶階層結構之基礎研究與應用;4.利用多巴胺製作無基材選擇表面抗沾粘修飾技術。 本計畫將建立新型雙離子表面修飾材Cys-b，應用於標靶型奈米複合光動藥劑，結合高光熱轉換之奈米材料與先進表面化學，從材料設計、基礎物理化學探討到生醫應用。此外，我們也將建立離子分子自組裝之學理，提供應變式智慧型生物界面原子結構之基礎。此研究將提升奈米醫學與生醫材料的進步與發展。最後，本計畫將廣泛地影響醫療產業核心技術的建立與高階人才的培養。 ;Surface self-assembling modifier for nanomaterials provides facile and effective approach to fine tune physicochemical interfacial properties, keep good colloidal stability, enable bio-functionalization and possess environmental responsiveness. However, conventional modifiers based on poly(ethylene glycol) (PEG) are susceptible to high temperature and ionic strength, leading to loss of hydration, non-specific adsorption and colloidal aggregation. These problems hamper wide applications of nanomaterials. In this proposal, we will develop a novel bioinspired zwitterionic cysteine betaine (Cys-b) as a surface modifier. Cys-b will be applied to hollow Ag@Au nanoshells as functional hyperthermia agent for targeted delivery to HER2-positive MDA-MB-453 breast cancer cells for hyperthermia treatment. The agent comprises of with strong absorption in a NIR range and bioinspired zwitterionic cysteine betaine (Cys-b) ligand. The hypothesis bases on the fact that the hydration mechanism of PEG-based relies on hydrogen bonding that is unstable at a high temperature, while that of zwitterionic materials on ionic solvation that is insensible to heat. In other words, the Cys-b adsorbates can afford effective antifouling properties, chemical and colloidal stability under the hyperthermia conditions. Therefore, we will prove the targeted therapeutic effect of the anti-HER2 antibody-conjugated Cys-b nanoshells for breast cancer cells. The research will be realized by three directions: 1.synthesis and physicochemical characterization of Cys-b and nanoshells; 2. Development of hyperthermia agent based on Cys-b nanoshells for breast cancer cells; 3. Fundamental investigation and applications of responsive 2D hierarchical Cys-b assemblies; 4. Development of substrate-independent antifouling coatings based on polydopamine. The aim of the study is to establish a novel zwitterionic surface ligand for targeting hyperthermia agent by integrating plasmonic nanomaterials and cutting-edge surface chemistry. The proposed work spams from material design, fundamental physicochemical investigation to biomedical applications. In addition, we will establish the theory of ionic self-assembly as a guiding principal for responsive intelligent biointerfaces. Such an approach sets the stage for advancement in biocompatibility, intelligence and versatility of medical devices. Though materials development, characterization and implementation, we will promote the fields of biomaterials science and technology, promote the core capability of biomedical industries and educate high-level researchers.
