光可調控溫度敏感型聚氮異丙基丙烯醯胺高分子的製 備及其細胞相容性

Preparation and cellular compatibility of optical-controlled thermo-responsive poly(N-isopropyl acrylamide)

張耿銘(Geng-Ming Zhang)

指導教授 ： 董崇民

淡江大學/工學院/化學工程與材料工程學系碩士班/碩士(2011年)

https://doi.org/10.6846/TKU.2011.00883

摘要

本研究主要是利用帶酸基之偶氮型起始劑4,4'-偶氮双(4-氰基戊酸)(4,4′-azobis(4-cyanovaleric acid), ACPA)起始聚合氮異丙基丙烯醯胺單體(N-isopropyl acrylamide, NIPAAm)，以形成末端具有酸基之聚氮異丙基丙烯醯胺(PNIPAAm-COOH)；經過70 oC反應12小時後，可得到分子量為6180的PNIPAAm-COOH。接著利用1-(3-二甲氨基丙基)-3-乙基碳二亞胺鹽酸鹽((N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride)與2-巰基乙胺鹽酸鹽(cysteamine hydrochloride)進行修飾，成為一硫醇封端聚氮-異丙基丙烯醯胺(PNIPAAm-SH)，硫醇封端基含量為28.32 μmole/g polymer，取代度為11.4%。另外利用種晶生成法合成出長37.23(±0.91) nm和寬11.15(±0.29) nm，長寬比值(aspect ratio, AR)為3.34，且形狀均一之奈米金桿(GNR)。最後將不同莫耳數的PNIPAAm-SH加入奈米金桿溶液中進行接枝反應以形成PNIPAAm接枝奈米金桿(PNIPAAm-GNR)。實驗結果發現以2.5 μmol之PNIPAAm-SH與4.64 nM的奈米金桿在30 oC進行接枝反應所形成之PNIPAAm接枝奈米金桿會有較佳之穩定性，經過5日後，最大吸收波長依然可維持在811 nm，吸光度一樣維持不變。並藉由STEM證實硫元素確實鍵結在奈米金桿表面，而在TEM影像顯示奈米金桿受到高分子鏈層層之保護。將此PNIPAAm-GNR溶液進行紅外光雷射引導(808 nm)及細胞培養等測試。測試結果顯示，LSCT在各階段(PNIPAAm-COOH、PNIPAAm-SH、PNIPAAm-GNR)皆無太大之改變，都在35 oC左右。PNIPAAm-AuR溶液經過近紅外光(808 nm, 500 mW)照射15分鐘後，由於奈米金桿的表面電漿共振效應(surface plasmon effect)，溫度可從27 oC上昇至45 oC，此溫度上昇進而引發PNIPAAm的相變化；同時此溫度敏感性行為在經過5次循環，仍具有可逆變化。PNIPAAm-GNR複合材料此複合材料不但具有光熱轉換之效應，且具可逆性，並且明顯改善原奈米金桿之生物毒性，細胞存活率從原先之1.07 %提升至89.0 %。

關鍵字

聚氮異丙基丙烯醯胺 ； 奈米金桿

並列摘要

In this study, 4,4'-azobis(4-cyanovaleric acid) (ACPA) was used to initiate polymerization of N-isopropyl acrylamide (NIPAAm) monomer in ethanol at 70oC to form carboxyl-terminated poly(N-isopropyl acrylamide) telechelic polymer (PNIPAAm-COOH). Subsequently, N-(3-dimethylaminopropyl)-N'-ethylcarbo- diimide hydrochloride and 2-mercapto-ethylamine hydrochloride (cysteamine hydrochloride) were chosen to modify the PNIPAAm-COOH to prepare thiol-end-capped poly(N-isopropyl acrylamide) (PNIPAAm-SH) , SH-functionalized content of 28.32 μmole/g polymer, instead of 11.4 %. In addition, nano-sized gold rod (GNR) was synthesized via the well-known seed-mediated method. The synthesized GNR was very uniform and had a dimension of 37.23(±0.91) nm in length and 11.15(±0.29) nm in width, thus having an aspect ratio (AR) of 3.34. Finally, PNIPAAm-SH with different amounts was added to the GNR solution to produce PNIPAAm-g-GNR composite. It was found the PNIPAAm-g-GNR solution prepared by grafting 2.5 μmol PNIPAAm-SH onto 4.64 nM of GNR solution at 30 oC had a superior stability. STEM results confirmed that the thiol group bonded onto the surface of gold nanorod, and the TEM image showed that the gold nanorod was protected by multi-layers of PNIPAAm chains. The PNIPAAm-g-GNR solution was tested for the near-IR irradiation-induced thermo-responsibility and cell compatibility. The results showed that all PNIPAAm-COOH, PNIPAAm-SH and PNIPAAm-g-GNR had the same LSCT at about 35 oC. Because of the surface plasmon effect of gold nanorod, the irradiation of near-IR at 808 nm for 15 minutes could induce the temperature rise from 27 oC to 45 oC. The thermo-responsibility was also reversible during five test cycles. Moreover, the PNIPAAm protection layer could decrease the cytotoxicity of the gold nanorod. The Cell Viability of 1.07 % from the previous increase to 89.0 %.

並列關鍵字

PNIPAAM ； Gold nanorod

參考文獻

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