在本研究中，於 pH 3.0 溶液中， poly(acrylic acid-co-2-methacryloylethyl acrylate)-g- poly(N-isopropylacrylamide) (poly(AAc-co-MEA)-g-PNIPAAm) (Copolymer A)及 poly(acrylic acid-co-2-methacryloylethyl acrylate)-g- poly(N-isopropylacrylamide)-g-monomethoxy poly(ethylene glycol) (poly(AAc-co-MEA)-g-PNIPAAm-g-mPEG) (Copolymer B)藉由未解離 的 AAc 單元與 NIPAAm 單元形成氫鍵，進而自組裝形成高分子液胞結構。高分子液胞膜 中的 MEA 單元進一步以光起始法進行交聯。此外，可藉由改變溶液的酸鹼值或溫度調控
交聯式高分子液胞組裝的結構。抗癌藥物 Doxorubicin (DOX)為一正電荷分子，其與液胞 上解離的 AAc 單元形成複合(Complexation)並與 NIPAAm 單元形成氫鍵，以達到高效率的
藥物包覆。由體外藥物釋放、細胞吞噬及細胞毒性測試結果可知，含 DOX 的高分子液胞 可於 HeLa 細胞內的酸性環境(如 lysosomes)中快速釋放藥物，以提高毒殺腫瘤細胞的效
果。上述結果顯示，此具酸鹼/溫度應答之高分子液胞組裝極具潛力應用於胞內的藥物傳 遞系統。
另一方面，Copolymer B 中未解離的 AAc 單元與檸檬酸化的奈米氧化鐵粒子(citric acid-modified iron oxide nanoparticles, IOPs)於 pH 3.0 溶液中會形成氫鍵，再於 60oC 下使 MEA 單元聚合，而得到 copolymer-caged IOPs (CCIOPs)。此交聯式 CCIOPs 的粒徑為 200
nm 並具有超順磁特性。此外，其藥物包覆率高達 88.3%，且具酸鹼應答的藥物釋放行 為。值得注意地，藉由改變酸鹼值，交聯式 CCIOPs 的橫向鬆弛率(r 2 )可被顯著的提升。交
聯式 CCIOPs 被 HeLa 細胞吞噬後(經由 endocytosis)，於 MR 影像中仍顯示為 dark imaging。此交聯式 CCIOPs 的體外細胞毒性測試結果顯示此載體可作為腫瘤細胞的診治平 台。

In this study, stimuli-responsive polymersomes were developed from spontaneous co-association of two graft copolymers both comprising acrylic acid (AAc) and 2-methacryloylethyl acrylate (MEA) units as the backbone and either poly(N-isopropylacrylamide) (PNIPAAm) alone (copolymer A) or both PNIPAAm and monomethoxy poly(ethylene glycol) (mPEG) chain segments as the grafts (copolymer B) via hydrogen bonding of unionized AAc with NIPAAm moieties with medium pH being
lowered from 7.4 to 3.0 at 25 oC. The PAAc/PNIPAAm-rich hydrophobic membranes of polymersomes were further cross-linked upon photo-initiated radical polymerization of
the MEA units. The cross-linked (CL) polymersomes exhibited an obvious structural regulation in response to changes in external pH and temperature. In addition, through hydrophobic AAc/doxorubicin (DOX) complexes formed via complementary electrostatic
attraction of DOX molecules with ionized AAc residues and then stabilized by hydrogen bonding between DOX and PNIPAAm, DOX was successfully encapsulated into CL
polymersomes. These results of in vitro drug release, cellular uptake and cytotoxicity indicate that after being internalized by HeLa cells via endocytosis, DOX-loaded CL polymersomes are capable of releasing rapidly drug within acidic endosomes and lysosomes upon extensive disruption of the originally formed electrostatic attraction and hydrogen bonding, thereby resulting in a high intracellular drug concentration to maintain therapeutic efficacy for anticancer treatment. Therefore, such polymersomes with pH- and thermo-responsive CL membranes show great potentiality of effective intracellular DOX delivery.
On the other hand, to develop multifunctional polymeric assemblies for drug delivery and enhanced MR imaging, through co-association of citric acid-modified iron oxide nanoparticles (IOPs) with copolymer B via extensive hydrogen bonding of
unionized carboxyl acid and NIPAAm residues with medium pH being adjusted from pH 7.4 to pH 3.0, the copolymer-caged IOPs (CCIOPs) were attained and then cross-linked
upon photo-initiated radical polymerization of the MEA units. The obtained cross-linked (CL) CCIOPs have a particles size of ca. 200 nm in diameter and superparamagnetic property. Moreover, the CL CCIOPs with a high DOX payload (ca. 88.3 %) exhibit superior pH-controlled drug release profiles. Interestingly enough, the transverse relaxivity (r 2 ) of the CL CCIOPs was appreciably enhanced and changed by varying external solution pH. After being internalized by HeLa cells via endocytosis, the CL
CCIOPs still showed significantly dark images. The results of in vitro cytotoxicity of CL CCIOPs further illustrate their potential application as a theranostic platform.

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