Palanikumar L, Kim Jimin, Oh Jun Yong, Choi Huyeon, Park Myoung-Hwan, Kim Chaekyu, Ryu Ja-Hyoung
Department of Chemistry, School of Natural Science, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.
Department of Chemistry, Sahmyook University, Seoul 01795, Republic of Korea.
ACS Biomater Sci Eng. 2018 May 14;4(5):1716-1722. doi: 10.1021/acsbiomaterials.8b00218. Epub 2018 Apr 6.
Systemic administration of mesoporous silica nanoparticles (MSNs) in biomedical applications has recently been questioned because of poor degradability, which is necessary for the successful development of new drug-delivery systems. Herein, we report the development of colloidal-state-degradable MSNs functionalized with versatile polymer-gatekeepers with a cancer-cell-targeted moiety. The polymer MSNs (PMSNs) were designed with disulfide cross-linking enabling safe encapsulation until cargos are delivered to target cancer cells. Selective targeting was achieved by decoration of CD44-receptor-targeting ligands, hyaluronic acid (HA), with HA-PMSNs. The selective cellular uptake mechanism of the fabricated targeted nanocarrier into CD44-overexpressed cancer cells was demonstrated through the clathrin- and macropinocytosis-mediated pathways. Upon internalization into cancer cells, doxorubicin loaded into the HA-PMSNs can be released by degradation of the polymer shells in the reducing intracellular microenvironment that consequentially induces cell death and further degradation of the MSNs. This study offers a simple technique to fabricate a versatile drug carrier with a high drug loading capacity.
由于可降解性差，介孔二氧化硅纳米颗粒（MSNs）在生物医学应用中的全身给药近来受到质疑，而可降解性是新型药物递送系统成功开发所必需的。在此，我们报告了用具有癌细胞靶向部分的多功能聚合物守门人功能化的胶体态可降解MSNs的开发。聚合物MSNs（PMSNs）通过二硫键交联设计，能够在货物递送至靶癌细胞之前实现安全封装。通过用透明质酸（HA）修饰CD44受体靶向配体，实现了HA-PMSNs的选择性靶向。通过网格蛋白介导和巨胞饮作用介导的途径，证明了所制备的靶向纳米载体对CD44过表达癌细胞的选择性细胞摄取机制。内化进入癌细胞后，负载在HA-PMSNs中的阿霉素可通过聚合物壳在还原性细胞内微环境中的降解而释放，从而诱导细胞死亡并进一步降解MSNs。本研究提供了一种制备具有高载药量的多功能药物载体的简单技术。
