| 摘要: | 在此研究中，我們對於奈米劑型同時包覆抗癌藥物和量子點 (quantum dots, QDs) 之處方設計、生物成像和藥物傳遞做全面的探討，目的是為了整合診斷和治療。本實驗主要是探討兩種奈米劑型：奈米脂質結構載體 (nanostructured lipid carriers, NLCs) 和微脂粒 (liposomes)。奈米劑型的物化特性藉由測定粒徑大小、表面電位、形態學、分子環境、示差熱掃描分析儀 (differential scanning calorimetry, DSC) 和核磁共振 (nuclear magnetic resonance, NMR) 得知。對於奈米劑型在生物成像和藥物傳遞的應用上，分別評估了細胞毒性、細胞遷移、細胞攝入、在體內腫瘤即時監控和腫瘤累積藥物含量。首先選擇不同性質的量子點包埋於 NLCs 中，稱為 QDNLCs，包括脂溶性量子點 (L-QDs)、羧基功能修飾的量子點 (C-QDs) 和聚乙二醇修飾的量子點 (P-QDs)。對於黑色素癌細胞毒殺實驗經由奈米劑型包埋後是優於游離的 camptothecin。在生物成像實驗中，以C-QDNLCs 於腫瘤的螢光訊號可以維持至少 24 小時。在第二個部分則是研究以不同處方的微脂粒包埋 C-QDs。實驗結果發現帶正電微脂粒包埋 QDs 為最佳選擇，因為其具有藥物控釋能力，高腫瘤細胞毒殺能力，並具有顯著的細胞和實體腫瘤螢光標記。本研究評估包埋抗癌藥物和 QDs 的奈米劑型系統做為一種新的多功能載體，並能同時達到治療及診斷的目的且深具未來發展潛力。
In this report, we comprehensively studied the formulation design, bioimaging, and delivery of drug-entrapped nanocarriers with quantum dots (QDs), for integrating diagnosis and therapy. This study is to use the two nanocarriers: nanostructured lipid carriers (NLCs) and liposomes. Nanocarriers were characterized by size, zeta potential, morphology, molecular environment, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). The application of the nanocarriers for imaging and drug delivery was evaluated by cytotoxicity, cell migration, cellular uptake, in vivo real-time tumor monitoring, anddrug accumulation in tumors. (Part I) Different QDs were selected to load with NLCs, which called QDNLC, including lipophilic QDs (L-QDs), carboxyl functioned QDs (C-QDs) and polyethylene glycol QDs (P-QDs). Cytotoxicity of the nanoparticles against melanoma cells was superior to that of free camptothecin. The real-time bioimaging demonstrated that C-QDNLCs could maintain the signaling in tumors for at least 24 h. (Part II) C-QDs was incorporated into different liposomes. Cationic quantum dot liposomes may be the best nanocarriers selected from this work because of their release, high cytotoxicity, and significant fluorescence labeling on cells and solid tumors. The drug-loaded nanocarriers with QDs evaluated in this study afford a new potential method for simultaneous therapeutic and diagnostic purposes. |
