理想的化療藥物載體應具有腫瘤標靶能力、低毒性並能夠有效治療具抗藥性之腫瘤組織。本研究中提出一兼具光觸發藥物釋放、磁場引導以及腫瘤分子影像功能之新式治療診斷奈米藥物載體。此載體主要組成為聚乳酸-甘醇酸共聚物，具有良好的生物相容性及生物可降解性，此高分子材料已通過美國食品藥物管理局(FDA)核准於臨床醫學使用，使用PLGA奈米粒子作為藥物傳遞的載體具有保護藥物活性、降低藥物毒性及改善藥物於水溶液中穩定性等優點。本研究中應用單層乳化法，已成功地將化療藥物阿黴素(doxorubicin，DOX)、超順磁氧化鐵奈米粒子(SPIONs)及具有光熱效應的金奈米棒(Au NRs)同時包覆於PLGA奈米粒子的疏水核心中，得到粒徑約為200 nm；表面電位為- 24 mV的氧化鐵奈米粒子/金奈米棒/阿黴素/聚乳酸-甘醇酸奈米粒子(DOX@SPIONs/ Au NRs/ PLGA nanoparticle, DOX@SAPP)。
經實驗證實，DOX@SAPP具有以下特點:親水性表面---外層覆蓋親水性聚乙二醇高分子(PEG)，有助於維持粒子分散性與延長其於生物體內之循環時間；高裝載效率---藥物包覆量約為3.77 %； SPIONs包覆量約為5.8 %，透過加入O.D值分別為33、100、300金奈米棒濃度可得到1.31 %、2.73 %及8.19 %的裝載效率；良好的穩定性---將載體系統分散於水、PBS、25 % FBS DMEM、100 % FBS等溶液中，三日內皆呈現優良的穩定性，在PBS中更穩定分散長達十五日以上；磁導引及腫瘤分子影像---該載體具超順磁特性，其飽和磁化量為3.04 emu/g，外加磁場下可成功吸引並累積於腫瘤細胞周邊，內吞載體的細胞可產生良好的MRI對比影像。透過細胞測試結果發現，DOX@SAPP可透過細胞內吞途徑(endocytosis)克服抗藥性細胞株不易累積藥物的限制，於外加磁場下可進一步提高細胞內載體累積量。於適當波長之雷射照射下，金奈米棒所產生之光熱效應可超越PLGA的玻璃轉換溫度(49˚C)，促使藥物迅速釋放，結果顯示所開發的DOX@SAPP兼具光熱與化學合併治療效應對於腫瘤細胞有極佳之殺傷力，並成功克服傳統化療藥物於治療抗藥性癌細胞上的限制。

An ideal carrier for chemotherapeutics delivery shall contain features such as cancer cell-targeting capability, low cytotoxicity and efficient killing effect on multiple drug resistant cancer cells. In this study, we proposed a novel nano-sized drug delivery system combining the advantages of: (1) NIR-triggered drug release; (2) magnetically-targeting and (3) magnetic resonance imaging (MRI) contrast. The drug carrier is mainly composed of poly-lactic-co-glycolic acid (PLGA), which is a highly biocompatible, biodegradable and US Food and Drug Administration (FDA)-approved materials for clinical uses. PLGA is widely used for drug delivery applications due to its advantages on protecting drug from loss of activity, reducing drug-associated cytotoxicity and improving drug stability. By utilizing single emulsion method, we have successfully encapsulated doxorubicin (a chemotherapeutic drug), superparamagnetic iron oxide nanoparticles (SPIONs) and gold nanorods (Au NRs) within the hydrophobic core of PLGA nanoparticles (NP). The size and surface potential of the resultant AFP were approximately 200 nm
and -24 mV respectively.
The prepared DOX@SPIONs/Au NRs/ PLGA nanoparticle(DOX@SAPP)were successfully verified with the following features, including: (1) Hydrophilic nanoparticle surface: the DOX@SAPP were covered with hydrophilic polyethylene glycol (PEG), which helps maintaining particle stability and may extend its in vivo circulation time. (2) Capability of loading of various theranostic materials: The loading contents for doxorubicin, SPIONs were 3.77% and 5.8% respectively. By tuning the feeding amount of dodecane-Au NRs (O.D. value 33, 100 and 300), PLGA nanoparticles with different Au NRs loading content (1.31%, 2.73% and 8.19%) can be prepared. (3) Well colloidal stability: the prepared DOX@SAPP were stable up to 3 days in various mediums such as: water, PBS and 25% FBS DMEM medium. The size of DOX@SAPP was not changed significantly in PBS for 15 days. (4) Magnetically-assisted drug delivery and MRI contrast: the DOX@SAPP exhibits superparamagnetism with the saturation magnetization of 3.04 emu/g. The cellular uptake of DOX@SAPP was greatly enhanced by the presence of external magnetic field. Cell-number dependent T2-weighing MRI was demonstrated from the DOX@SAPP -uptake cancer cells. The DOX@SAPP enters cells via endocytosis which can avoid the “drug pumping out” effect by multiple drug resistant cancer cells. Under the irradiation of NIR, the Au NRs-mediated photothermal effect effectively triggered rapid drug release from DOX@SAPP Finally, the combined photothermal- and chemo- therapeutic effect was successfully demonstrated on astrocytoma tumor cell line (ALTS1C1), human breast cancer cells (MCF7) and its multiple drug resistant strain (ADR-MCF7).

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