本計畫是開發一種同時具有產生四合一功能(氧氣功能、光熱治療、光動力治療、化學治療)的奈米複合材料(過氧化鈣/海藻膠/金奈米棒)作為藥物載體與腫瘤治療平台。當過氧化鈣/海藻膠/金奈米棒包覆抗癌藥物和光敏劑後，可以改善現有光動力治療因為腫瘤的缺氧微環境所導致的低效率治療效果。因為缺氧環境會讓腫瘤區域產生大量的缺氧誘導因子而誘發進行血管新生及腫瘤細胞轉移的行為，同時缺氧誘導因子也是啟動與腫瘤細胞生長相關因子的源頭。因此本計畫利用過氧化鈣/海藻膠/金奈米棒複合材料所產生的氧氣來抑制缺氧環境進而抑制腫瘤細胞的生長，產生的氧氣同時可供給光敏劑產生足量單氧進而提高光動力治療效綠。結合光熱治療、光動力治療、化學治療的協同治療策略可以達到比現有單一使用光動力治療、光熱治療或化學治療具有更高效率的腫瘤治療效果。另外，過氧化鈣/海藻膠/金奈米棒複合材料可以做為斷層掃描的顯影劑，提供分子影像功能。本計畫所提出之改善腫瘤缺氧微環境並結合藥物載體、光熱治療和光動力治療的協同治療策略，是一種具新穎性且有潛力的治療策略，不僅可以改善現有光動力治療所遭遇的問題與困難，更可以增益光動力治療產生更高效率的治療效果。
The purpose of this project is to synthesize a multifunctional nanocomposite (calcium peroxide/alginate/Au nanorods) with functions of oxygen generation, photothermal therapy and photodynamic therapy. Calcium peroxide/alginate/Au nanorods can be as a drug carrier and therapeutic platform of cancer. Anti-cancer drug (doxorubicin) and photosensitizer (indocyanine green)-encapsulated calcium peroxide/alginate/Au nanorods can improve the therapeutic efficiency of photodynamic therapy which has the limited therapeutic efficiency in hypoxia microenvironment of cancer. Hypoxia microenvironment can induce cancer cells to overexpress hypoxia-induced factor-1 (HIF-1) that can induce angiogenesis and cancer cell migration. At the same time, HIF-1 is also an important factor that can increase the expression of proteins which related to growth pathways of cancer cells. This project will use calcium peroxide/alginate/Au nanorods to generate oxygen to overcome the hypoxia microenvironment and then inhibit the growth of cancer cells. The generated oxygen also can make ICG produce more singlet oxygen and then enhance the therapeutic efficiency of photodynamic therapy. Combination of photothermal, photodynamic, and chemo therapies can have a synergistic effect to promote higher therapeutic efficacy as compared to use of only one strategy among three therapeutic strategies. Furthermore, the calcium peroxide /alginate/Au nanorods can provide the function of molecular imaging (computed tomography，CT). In this project, the synergistic therapy of changing tumor hypoxia microenvironment and combining photothermal, photodynamic, and chemo therapies to treat tumor disease is a novel and innovative therapeutic strategy. This synergistic therapy not only improves the problems of current therapeutic therapy but also enhances its therapeutic efficiency of photodynamic therapy.
