自組裝脂質樣碳奈米點應用於癌症治療

Abstract

癌症是全球第二大死亡原因，其中腫瘤轉移是臨床癌症病患的的主要死因，佔所有癌症患者的90%以上。不幸的是，目前針對轉移癌的治療策略有很大的局限性，致使發展能夠特異性靶向標靶轉移癌的新療法乃是現今癌症治療的亮點。在這份研究中，我們通過簡單的乾燥鍛燒與水解的方法成功合成了一種新型的脂質樣碳奈米點(Lipid-like C-dots)，它可以自組裝成類微脂體的結構，即碳奈米點微脂體（CDsomes）。為了克服癌症轉移，在本研究第一部分中，我們首先評估了CDsomes本身的對於癌症細胞治療效果。我們發現 CDsomes可以驅動光催化級聯反應以產生足夠量的氧化壓力來殺死癌細胞。特別的是，我們發現其光催化級聯反應的機理與其獨特的螢光開關切換特性高度相關。研究的第二部分則通過一系列細胞遷移實驗來評估CDsomes的抗癌轉移能力，在這一部分中，我們發現CDsomes可以專一性累積於細胞膜上，並通過在腫瘤環境中誘導膜脂質進行排列從而降低轉移性癌細胞膜的流動性，降低細胞膜流動性不僅在動物體外測試中顯著抑制了轉移細胞的遷移和侵襲浸潤能力，而且在動物體內明顯阻止了腫瘤的轉移。除此之外CDsomse可以有效地攜帶一系列不同極性的抗癌藥物，並將它們輸送到高度異質腫瘤的深層區域。總的來說，我們的研究結果表明，CDsomes不僅可以作為光動力療法的光敏劑，而且還提供了一種簡單而有效的策略來增加提攜帶藥物的療效和防止細胞移動，從而減少癌症轉移。

Cancer is the second leading cause of death worldwide. Tumor metastasis is the major cause modality in clinical cancer treatments, accounting for over 90% of all cancer patients. Unfortunately, current therapeutic strategies toward metastasis cancer have significant limitations, and there is great interest in aspiring novel therapies capable of specifically targeting metastasis cancer. In this report, a novel lipid-like C-dots were synthesized through a simple dry heat route followed by hydrolysis, which can self-assemble into a liposome-like structure, namely C-dot liposome (CDsomes). To overcome cancer metastasis, the therapeutic effects of CDsomes itself were evaluated in the first part. We found that the CDsomes can drive a photocatalytic cascade reaction to produce a sufficient amount of oxidative stress for killing cancer cells. The mechanism of photocatalytic cascade reaction is highly correlated with its unique photoswitching property. In the second part, the anticancer metastasis of CDsomes was evaluated by a series of cell mobility tests. In this part, CDsomes are found to target the cell membrane and subsequently down-regulated the cell membrane fluidity by ordering the membrane lipid, epically in an acidic tumor environment. The down-regulated cell membrane fluidity dramatically not only inhibits the metastatic cell migration and invasion in vitro but obviously prevents the tumor metastasis in vivo. Moreover, the CDsomse can efficiently carry a series of anticancer drugs with different polarities meanwhile deliver them to a deep region of a heterogenic tumor. Collectively, our findings suggest that CDsomes can not only serve as a photosensitizer for photodynamic therapy but also provide a simple but effective strategy to enhance medical performance and prevent cellular mobility that reduces cancer metastasis.