功能性奈米載體於癌症細胞生物行為之研究

Abstract

控制藥物釋放系統在全球已經引起各界高度的關注，尤其是在可受外力場刺激，以及具靶向作用之智慧型藥物釋放系統更為大家所重視。在此研究中，合成具多功能殼核型奈米藥物輸送載體，其中包載抗癌藥劑Camptothecin，並且能夠藉由外加磁場作為驅動力，有效地控制其藥物釋放的行為。油溶性的藥物被包覆在氧化鐵與高分子所形成的核中，外面包覆一層薄薄的二氧化矽，這樣的結構設計，能有效調控並防止藥物達作用前的流失。在外在磁場的刺激(非接觸性)下，核內物質發生結構上的變化，藥物能快速地由載體中釋放出來。此外，本實驗更進一步於奈米載體表面嫁接上anti-EGFR，以EGFR過度表現的癌症細胞作為靶向。令人驚喜的是，這種不含界面活性劑的奈米藥物載體擁有相當好的生物相容性，並能快速有效的進入肺癌細胞中(A549)，其進入細胞的機制主要為macropinocytosis 和clathrin-mediated endocytosis。此奈米載體除了能有效受磁場控制的特性外，在癌症細胞的治療以及作用上亦展現了多種優勢：同時具有靶向標定、熱治療、化療以及細胞顯影等功能。在此研究中，我們以非小細胞肺癌為對象，設計了具多種治療效果的靶向奈米藥物載體，並於in vitro 實驗中作進一步的探討與評估。

Controlled drug released has been received greatest attention worldwide, especially cell-specific targeted or stimuli-responsive drug delivery systems. In this study, drug-containing iron oxide/silica core–shell (SAIO@SiO2) nanocarriers were synthesized as a multifunctional drug delivery nanosystem where the drug, CPT, a highly potent anti-cancer substance, can be effectively triggered with a controllable release pattern by an external magnetic field. The hydrophobic drug (CPT) molecules were encapsulated within the iron oxide-PVA core and then further covered with a thin-layer silica shell to regulate the release pattern, where un-desirable release or leakage can be effectively inhibited. The SAIO@SiO2@AE nanocarriers were coupled with an anti-EGFR on the surface of SAIO@SiO2 nanocarriers in order to target to EGFR overexpressed cancer cells. Remote control of drug release from the SAIO@SiO2 nanocarriers was achieved successfully using an external magnetic field where the core phase being structurally disintegrated to a certain extent while subjecting to magnetic stimulus, resulting in a burst release of the encapsulated drug. Surprisingly, the surfactant-free SAIO@SiO2 and SAIO@SiO2@AE nanocarriers demonstrated excellent cytocompatibility and high uptake efficiency by the A549 cell line within short time through energy-dependent macropinocytosis and clathrin-mediated endocytosis. Together with a well-regulated controlled release design, the nanocarriers provide great advantages as an effective cell-based drug delivery nanosystem on cell-targeting, hyperthermia, chemotherapy and cellular image for anti-cancer applications. In this report, we show a stepwise study of a nanocarriers-based multifunctional targeted delivery system for in vitro therapeutic application in non small cell lung cancer.