Srinivasan Supriya, Bhardwaj Vinay, Nagasetti Abhignyan, Fernandez-Fernandez Alicia, McGoron Anthony J
J Biomed Nanotechnol. 2016 Dec;12(12):2202-19. doi: 10.1166/jbn.2016.2312.
This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.
本研究论文报道了一种基于银纳米颗粒的多功能抗癌前药系统的研发。该前药系统由尺寸为70纳米的纳米颗粒组成，具有光动力治疗特性以及活性、pH触发的药物释放功能。银纳米颗粒通过酰胺键修饰有叶酸（FA）靶向配体，并且还通过酸可裂解的腙键与化疗药物阿霉素（DOX）共轭。FA和DOX都通过聚乙二醇（PEG）间隔基连接到银纳米颗粒上。这种前药系统可以优先进入过度表达叶酸受体的细胞，随后通过细胞内pH降低触发细胞内药物释放。此外，银纳米颗粒载体系统具有光动力治疗（PDT）活性，因此在光照下，过度表达叶酸受体的癌细胞的细胞活力可以进一步降低。pH触发的药物释放和PDT的双重作用提高了该系统的治疗效果。多功能纳米颗粒可以通过表面增强拉曼光谱（SERS）和荧光光谱在细胞内进行探测。本报告探讨了这种基于多功能银纳米颗粒的系统在癌症诊疗中的适用性。
