Lian Huibo, Wu Jinhui, Hu Yiqiao, Guo Hongqian
Department of Urology, Drum Tower Hospital, Medical School of Nanjing University.
State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, Jiangsu, People's Republic of China.
Int J Nanomedicine. 2017 Oct 24;12:7777-7787. doi: 10.2147/IJN.S144634. eCollection 2017.
Resistance to regular treatment strategies is a big challenge in the treatment of castration-resistant prostate cancer. Combination of photothermal and photodynamic therapy (PTT/PDT) with chemotherapy offers unique advantages over monotherapy alone. However, free drugs, such as photosensitizers and chemotherapeutic agents, lack tumor-targeted accumulation and can be easily eliminated from the body. Moreover, most of the PTT drugs are hydrophobic and their organic solvents have in vivo toxicity, thereby limiting their potential in clinical translation. Herein, simple multifunctional nanoparticles (NPs) using IR780 (a near-infrared dye) and docetaxel (DTX)-loaded nanoplatform based on human serum albumin (HSA) (HSA@IR780@DTX) was developed for targeted imaging and for PTT/PDT with chemotherapy for the treatment of castration-resistant prostate cancer treatment. In this platform, HSA is a biocompatible nanocarrier that binds to both DTX and IR780. DTX and IR780, as hydrophobic drug, can induce the self-assembly of HSA proteins. Transmission electron microscopic imaging showed that NPs formed by self-assembly are spherical with a smooth surface with a hydrodynamic diameter of 146.5±10.8 nm. The cytotoxicity of HSA@IR780@DTX NPs with or without laser irradiation in prostate cancer cells (22RV1) was determined via CCK-8 assay. The antitumor effect of HSA@IR780@DTX plus laser irradiation was better than either HSA@IR780@DTX without laser exposure or single PTT heating induced by HSA@IR780 NPs under near-infrared laser, suggesting a significant combined effect in comparison to monotherapy. Near-infrared fluorescence imaging showed that HSA@IR780@DTX NPs could preferentially accumulate in tumors. In vivo therapeutic efficacy experiment showed that xenografted prostate tumors on mice treated with HSA@IR780@DTX plus near-infrared laser irradiation were completely inhibited, whereas tumors on mice treated with chemotherapy alone (HSA@DTX and HSA@IR780@DTX without laser) or PTT/PDT alone (HSA@IR780 with laser) showed moderate growth inhibition. Overall, HSA@IR780@DTX NPs showed notable targeting and theranostic potential for the treatment of castration-resistant prostate cancer.
对常规治疗策略产生耐药性是去势抵抗性前列腺癌治疗中的一大挑战。光热疗法和光动力疗法（PTT/PDT）与化疗联合使用比单独的单一疗法具有独特优势。然而，游离药物，如光敏剂和化疗药物，缺乏肿瘤靶向性聚集，且容易从体内清除。此外，大多数PTT药物具有疏水性，其有机溶剂具有体内毒性，从而限制了它们在临床转化中的潜力。在此，基于人血清白蛋白（HSA）开发了一种简单的多功能纳米颗粒（NPs），其负载有IR780（一种近红外染料）和多西他赛（DTX）（HSA@IR780@DTX），用于靶向成像以及用于PTT/PDT联合化疗来治疗去势抵抗性前列腺癌。在这个平台中，HSA是一种生物相容性纳米载体，它能与DTX和IR780结合。DTX和IR780作为疏水性药物，可诱导HSA蛋白的自组装。透射电子显微镜成像显示，通过自组装形成的纳米颗粒呈球形，表面光滑，流体动力学直径为146.5±10.8纳米。通过CCK-8测定法确定了有或无激光照射时HSA@IR780@DTX纳米颗粒对前列腺癌细胞（22RV1）的细胞毒性。HSA@IR780@DTX加激光照射的抗肿瘤效果优于未进行激光照射的HSA@IR780@DTX或近红外激光照射下HSA@IR780纳米颗粒诱导的单一PTT加热，表明与单一疗法相比有显著的联合效果。近红外荧光成像显示，HSA@IR780@DTX纳米颗粒可优先在肿瘤中聚集。体内治疗效果实验表明，接受HSA@IR780@DTX加近红外激光照射治疗的小鼠体内移植的前列腺肿瘤被完全抑制，而单独接受化疗（HSA@DTX和未进行激光照射的HSA@IR780@DTX）或单独接受PTT/PDT（进行激光照射的HSA@IR780）治疗的小鼠肿瘤生长受到中度抑制。总体而言，HSA@IR780@DTX纳米颗粒在治疗去势抵抗性前列腺癌方面显示出显著的靶向性和诊疗潜力。
