School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, No. 280, Waihuandong Road, Education Mega Centre, 510006, Guangzhou, China.
School of Pharmacy, Guangdong Pharmaceutical University, No. 280, Waihuandong Road, Education Mega Centre, 510006, Guangzhou, China.
J Mater Sci Mater Med. 2019 Jun 19;30(7):76. doi: 10.1007/s10856-019-6278-y.
Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.
超顺磁性氧化铁纳米粒子（SPION）由于其独特的磁性和易于表面修饰的特性，被广泛用作靶向药物输送平台。然而，SPION 在精准医学中的靶向准确性不足仍然是一个巨大的障碍。在此，通过连接适体杂交核酸结构来增强 SPION 的肿瘤靶向性。修饰在 SPION 表面的适体由双链 DNA（dsDNA）和 G-四链体 DNA（AS1411）结构组成，分别携带一种化学抗癌药物柔红霉素（DNM）和一种光敏剂分子，即 5,10,15,20-四（苯基-4-N-甲基-4-吡啶基）卟啉（TMPyP）。与适体-dsDNA 共轭的 SPION 纳米载体（命名为 Apt-S8@SPION）在血清中和核酸酶 DNase I 中表现出良好的稳定性。载药纳米载体（TMPyP&DNM&Apt-S8@SPION）对 A549 和 C26 细胞（代表核仁素过表达的癌细胞）具有高细胞毒性。核仁素阻断实验明确表明，形成的纳米药物可以通过特定的 AS1411-核仁素相互作用靶向细胞表面，从而增加细胞摄取效率。同时，TMPyP&DNM&Apt-S8@SPION 纳米球可以通过可见光照射有效地产生细胞毒性活性氧，从而建立一种新型的光动力疗法来治疗癌细胞。因此，设计的 TMPyP&DNM&Apt-S8@SPION 纳米粒子具有磁适体双重靶向和联合化学-光动力治疗的作用，有望成为精准医学时代理想的药物输送载体，具有巨大的潜力。
