合成並探討PEGMA-co-DPA奈米粒子之特性及其在光動力療法上之應用

Abstract

光動力療法(PDT)是一個有效治療腫瘤的方法，其方法是給予光感藥物後再照光以達到療效。然而，光感藥物有著不溶於水且對腫瘤沒有選擇性的缺點。為了以在腫瘤中的酸性環境為目標，我們使用AIBN為initiator合成了PEGMA-co-DPA這個分子聚合物，並以此聚合物做成了對酸鹼值敏感的奈米粒子來包覆光感藥物-間–四羥基氯苯酚 (m-THPC)。我們使用核磁共振儀及凝膠滲透層析來分析我們合成的分子聚合物，並使用pyrene作為探針來研究酸鹼度對於次分子聚合物形成奈米粒子和其臨界聚合濃度(CAC)的影響。結果顯示在此合成的分子聚合物的臨界聚合酸鹼值在5.8到6.6之間，臨界聚合濃度則是在0.0045%到0.0089%之間。之後我們以oil-in-water的方式製備了包覆m-THPC的奈米粒子，並使用動態光散射儀(DLS)以及穿透式電子顯微鏡(TEM)觀察奈米粒子，發現此奈米粒子為圓形且大小約為132奈米，包覆率為89%。在釋放速率的實驗方面，結果顯示了放置48小時後，此奈米粒子在酸鹼值為5的環境下釋放了58%的藥物，比在酸鹼值為7的環境下的10%還多。另外我們使用HT-29這株細胞來研究此奈米粒子的光動力療法效果。以上這些結果顯示了我們製備的對酸鹼度敏感的奈米粒子有針對腫瘤的潛力。

Photodynamic therapy (PDT) is an effective therapy for tumor, which involves the administration of photosensitizers followed by illumination. However, the insolubility and non-targeting are defects of photosensitizers. For targeting the acid environment at tumor site, Poly(ethylene glycol) methacrylate-co-2-(Diisopropylamino) ethyl methacrylate (PEGMA-co-DPA) copolymers were synthesized in the presence of 2,2’-Azobis-isobutyronitrile (AIBN) and then formed pH sensitive nanoparticles to encapsulate a photosensitizer, m-THPC. The characteristic of these copolymers were evaluated by 1H nuclear magnetic resonance and gel permeation chromatography. The pH effect on aggregation/deaggregation and critical aggregation concentration (CAC) of the nanoparticles was studied by using pyrene as a probe. The results showed that the critical aggregation pH (Ph*) of the polymers were from 5.8 to 6.6 and the CAC were from 0.0045 to 0.0089 wt% at pH 7.4. The m-THPC loaded nanoparticles were prepared by oil-in-water. The size and morphology of nanoparticles were observed using dynamic light scattering and transmission electron microscopy. The results indicated that the nanoparticles were sphere and the size was 132 nm. The drug encapsulation efficiency was 89%. The in vitro release profile performed that the release rate of m-THPC at pH 5.0 (58% m-THPC released within 48 hours) was faster than at pH 7.0 (10% m-THPC released within 48 hours). The in vitro PDT efficiency was tested with HT-29 cell line by MTT assay. These findings suggest that the pH sensitive nanoparticles prepared in this study are potential carriers for tumor targeting.