Wu Zhi-Yuan, Lee Cheng-Chang, Lin Hsiu-Mei
Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung City 20224, Taiwan.
Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung City 20224, Taiwan.
Cancers (Basel). 2019 May 20;11(5):697. doi: 10.3390/cancers11050697.
Nanoparticle-based drug delivery systems are among the most popular research topics in recent years. Compared with traditional drug carriers, mesoporous silica nanoparticles (MSN) offer modifiable surfaces, adjustable pore sizes and good biocompatibility. Nanoparticle-based drug delivery systems have become a research direction for many scientists. With the active target factionalized, scientists could deliver drug carriers into cancer cells successfully. However, drugs in cancer cells could elicit drug resistance and induce cell exocytosis. Thus, the drug cannot be delivered to its pharmacological location, such as the nucleus. Therefore, binding the cell membrane and the nuclear target on the nanomaterial so that the anticancer drug can be delivered to its pharmacological action site is our goal. In this study, MSN-EuGd was synthesized by doping Eu and Gd during the synthesis of MSN. The surface of the material was then connected to the TAT peptide as the nucleus target for targeting the cancer nucleus and then loaded with the anticancer drug camptothecin (CPT). Then, the surface of MSN-EuGd was bonded to the hyaluronic acid as an active target and gatekeeper. With this system, it is possible and desirable to achieve dual imaging and dual targeting, as well as to deliver drugs to the cell nucleus under a hyaluronidase-controlled release. The experimental approach is divided into three parts. First, we conferred the material with fluorescent and magnetic dual-imaging property by doping Eu and Gd into the MSN. Second, modification of the cell membrane target molecule and the nucleus target molecule occurred on the surface of the nanoparticle, making the nanoparticle a target drug carrier. Third, the loading of drug molecules into the carrier gave the entire carrier a specific target profile and enabled the ability to treat cancer. In this study, we investigated the basic properties of the drug carrier, including physical properties, chemical properties, and in vitro tests. The result showed that we have successfully designed a drug delivery system that recognizes normal cells and cancer cells and has good anticancer effects.
基于纳米颗粒的药物递送系统是近年来最热门的研究课题之一。与传统药物载体相比，介孔二氧化硅纳米颗粒（MSN）具有可修饰的表面、可调节的孔径和良好的生物相容性。基于纳米颗粒的药物递送系统已成为许多科学家的一个研究方向。随着活性靶向部分的分化，科学家们能够成功地将药物载体输送到癌细胞中。然而，癌细胞中的药物可能会引发耐药性并诱导细胞胞吐作用。因此，药物无法被递送到其药理作用部位，如细胞核。因此，将细胞膜和核靶向结合在纳米材料上，使抗癌药物能够被递送到其药理作用部位是我们的目标。在本研究中，通过在MSN合成过程中掺杂Eu和Gd合成了MSN-EuGd。然后将该材料的表面连接到作为细胞核靶向的TAT肽上，用于靶向癌细胞核，接着负载抗癌药物喜树碱（CPT）。然后，将透明质酸作为活性靶向和守门人结合到MSN-EuGd的表面。利用该系统，实现双成像和双靶向以及在透明质酸酶控制释放下将药物递送到细胞核是可行且理想的。实验方法分为三个部分。首先，通过将Eu和Gd掺杂到MSN中赋予材料荧光和磁性双成像特性。其次，在纳米颗粒表面进行细胞膜靶向分子和细胞核靶向分子的修饰，使纳米颗粒成为靶向药物载体。第三，将药物分子负载到载体中，使整个载体具有特定的靶向特性并具备治疗癌症的能力。在本研究中，我们研究了药物载体的基本性质，包括物理性质、化学性质和体外测试。结果表明，我们成功设计了一种能够识别正常细胞和癌细胞且具有良好抗癌效果的药物递送系统。
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