摘要
兩性離子高分子是一種同時帶有陰、陽離子基團的聚合物，其具有極佳的親水性質、優良的熱與化學穩定性、生物相容性、抗污染性能和特殊的“反聚電解質效應”等特性，近幾年在抗污材料、物質檢測與藥物傳輸載體等應用領域有極高發展潛力，而金奈米粒子(gold nanoparticles，AuNPs)具有製備容易、良好生物適應性、特殊光學性質與容易進行表面修飾等優點。本研究在開發一具有高穩定性與生物相容性的金奈米載體，在設計上是將金奈米粒子修飾兩性離子高分子，以提高金奈米粒子於水中的分散性、穩定性與生物相容性，且用於載負光敏劑靛氰綠(Indocyanine green, ICG)可應用於光熱與光動力治療。 本實驗以原子轉移自由基聚合(Atom transfer radical polymerization, ATRP)，合成一系列具生物相容性與non-fouling的兩性離子高分子poly(sulfobetaine methacrylate) (PSBMA)。另外，以氧化還原法合成球型金奈米粒子，並藉由金硫鍵結(Au-S bonds)分別修飾於金奈米粒子表面，增加其分散性以及穩定性。接著利用核磁共振光譜儀(NMR)、膠體滲透層析儀(GPC)、紫外-可見光光譜儀(UV-Visible)、動態光散射粒徑分析儀(DLS)以及穿透式電子顯微鏡(TEM)等儀器鑑定PSBMA修飾之金奈米粒子(AuNPs-PSBMA)之性質。 此外，AuNPs-PSBMA在水溶液中與在牛血清白蛋白(BSA)溶液中穩定性測試，則於人體溫度37℃且持續追蹤其粒徑變化至少2個月，結果顯示修飾高分子之AuNPs-S200擁有極佳的分散與穩定性。最後將光敏劑靛青綠(Indocyanune green, ICG)負載於AuNPs-PSBMA，結果顯示AuNPs-S200不僅具有最高的ICG負載量，同時也有效改善了ICG於水溶液中的穩定度，這些結果都證實了ICG-AuNPs-S200具有應用於藥物載體之潛力。因此，我們也利用808 nm雷射光作為照射光源，在光熱實驗中檢測ICG所需最低濃度(於6 min內達42℃以上)，以及利用2’,7’-dichlorofluorescin diacetate (DCFH-DA)作為螢光指示劑，證明其具有單重態氧產生之能力，成功證實了兩性離子高分子金奈米載體具備光熱以及光動力治療的潛力。
並列摘要
Zwitterionic polymers with anionic and cationic groups simultaneously in the repeat unit, have excellent hydrophilic properties, excellent thermal and chemical stability, good bio-compatibility, non-fouling properties and special "antipolyelectrolyte effect". Gold nanoparticles (AuNPs) have several advantages, including easy fabrication and surface modification, good bio-compatibility, and special optical properties. In this study, we aim to develop the highly stable and bio-compatible AuNPs as drug-delivery carriers by grafting zwitterionic polymers on the surface of AuNPs. We expect the super hydrophilic and non-fouling properties of zwitterionic polymers can improve the stability and dispersion of zwitterionic polymers-grafted AuNPs in PBS and protein solution. Further, indocyanine green (ICG) was introduced into AuNPs-PSBMA through electrostatic interaction for investigation on its potential applications in photodynamic therapy (PDT) and photothermal therapy (PTT). In this study, a thiol initiator bis [2-(2'-bromoisobutyryloxy) ethyl] disulfide was used to synthesize poly(sulfobetaine methacrylate) (PSBMA) via atom transfer radical polymerization (ATRP). The prepared PSBMA-grafted AuNPs were characterized via dynamic light scattering (DLS), UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM). In addition, the stability of PSBMA-grafted AuNPs was monitored by DLS for two months in BSA protein solution at 37℃, showing AuNPs-S200 had the best dispersion and stability. Indocyanine green (ICG)-loaded AuNPs-PSBMA was investigated by DLS、UV-vis and TEM. The results showed ICG-AuNPs-S200 had the highest ICG loading content and improved the stability of ICG in aqueous solution. In addition, photothermal effect and efficiency of singlet oxygen generation were investigated under irradiation with 808 nm laser light. The results showed ICG-AuNPs-S200 could reach above 42 oC and 2’,7’-dichlorofluorescin diacetate (DCFH-DA) staining examination demonstated the singlet oxygen generated within Hela cells as treated with ICG-AuNPs-S200 under light irradiation. Therefore, ICG-AuNPs-S200 has the potential applications for PDT and PTT.
參考文獻
延伸閱讀
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