Shi Zhenzhi, Ren Wenzhi, Gong An, Zhao Xinmei, Zou Yuehong, Brown Eric Michael Bratsolias, Chen Xiaoyuan, Wu Aiguo
Key Laboratory of Magnetic Materials and Devices, & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.
Department of Biological Sciences, University of Wisconsin-Whitewater, Whitewater, WI 53190, USA.
Biomaterials. 2014 Aug;35(25):7058-67. doi: 10.1016/j.biomaterials.2014.04.105. Epub 2014 May 20.
Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm(2) for 0.5 min; low light dose = 25 mW/cm(2) for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors.
光动力疗法(PDT)是一种用于癌症和其他恶性疾病的很有前景的治疗方式,然而在其发挥全部潜力并得到更广泛的临床应用之前,仍需要提高安全性和疗效。在此,我们通过开发一种使用甲氧基聚(乙二醇)硫醇(mPEG-SH)修饰的金纳米棒(GNR)-磺化铝酞菁(AlPcS4)光敏剂复合物的高/低功率密度光动力疗法模式(高/低PDT模式),研究了一种高效且安全的光动力治疗程序。利用傅里叶变换红外光谱法验证了与简单聚电解质包覆的GNR表面共轭的mPEG-SH;这提高了稳定性,降低了细胞毒性,并提高了纳米颗粒分散体的包封率和负载效率。将GNR-光敏剂复合物置于高/低PDT模式下(高光照剂量 = 80 mW/cm²,持续0.5分钟;低光照剂量 = 25 mW/cm²,持续1.5分钟),高PDT疗效导致约90%的肿瘤细胞死亡。由于复合物具有协同的等离子体光热特性,高/低PDT模式比使用单波长连续激光照射显示出更高的疗效。此外,在相同照射条件下,暴露于游离AlPcS4光敏剂的细胞未观察到明显的活力损失。因此,在细胞进入之前从GNR释放的游离AlPcS4对正常细胞的细胞毒性没有影响,也没有对高功率密度激光的使用造成限制。这种高/低PDT模式可能有效地为浅表肿瘤带来更安全、更有效的光动力治疗。