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目的:研究荧光磁性纳米粒子与前列腺癌特异性抗原(prostate cancer specific antigen,PSA)单链抗体片段结合的复合纳米探针作为前列腺癌核磁共振靶向显像剂与治疗剂的可行性。方法:荧光磁性纳米粒子(FMCNPs)与前列腺癌特异性单链抗体片段(ScFv)桥联制备成复合纳米探针(FMCNPs-ScFv),应用高分辨电镜、荧光光谱仪与磁强度计进行鉴定。将FMCNPs-ScFv与前列腺癌LNCaP细胞共培养,观察其进入癌细胞的靶向性;采用MTT法评价复合纳米探针的细胞毒性。建立裸鼠前列腺癌细胞移植模型,进行免疫组化和病理学鉴定;荷前列腺癌裸鼠尾静脉注射复合纳米探针,采用荧光成像系统观察纳米探针在裸鼠体内的分布消除过程;利用核磁共振观察复合纳米探针肿瘤靶向显像效果;给予体外磁场照射(100W功率)30min,观察肿瘤体积的变化。结果:成功制备复合纳米探针FMCNPs-ScFv;细胞培养实验显示复合纳米探针能够进入前列腺癌细胞质;在显像浓度范围内复合纳米探针细胞毒性很低,不影响细胞增殖。成功制备裸鼠前列腺癌模型。荧光成像系统显示复合纳米探针快速地在裸鼠各重要器官分布,并逐渐集中于肿瘤部位;核磁共振显示纳米探针在24h内能够清晰显示前列腺癌图像;体外磁场照射4d后,注射复合纳米探针的裸鼠肿瘤组织生长显著慢于对照裸鼠的肿瘤组织(P<0.05)。结论:制备的复合纳米探针FMCNPs-ScFv能有效地靶向前列腺癌组织,可用于前列腺癌的核磁共振成像,也能用于体外磁场作用下的肿瘤治疗。
OBJECTIVE: To study the feasibility of using composite nano-probes with fluorescent magnetic nano-particles and single-chain antibody fragments of prostate cancer specific antigen (PSA) as targeted imaging agents and therapeutic agents for prostate cancer. METHODS: FMCNPs-FFs (FMCNPs-ScFv) were prepared by bridging with FMCNPs and PrFv, and were identified by high-resolution electron microscopy, fluorescence spectroscopy and magnetometer. The FMCNPs-ScFv were co-cultured with LNCaP prostate cancer cells to observe their targeting into cancer cells. The cytotoxicity of the composite nano-probes was evaluated by MTT assay. The nude mice model of prostate cancer cell transplantation was established and immunohistochemically and pathologically identified. The composite nano-probes were injected into tail vein of nude mice bearing prostate cancer. Fluorescence imaging system was used to observe the distribution and elimination of nano-probes in nude mice. Resonance observation of the composite nano-probe tumor targeted imaging effect; given in vitro magnetic field irradiation (100W power) 30min, observe the tumor volume changes. RESULTS: FMCNPs-ScFv was successfully prepared. Cell-culture experiments showed that the composite nano-probes could enter the cytoplasm of prostate cancer. The composite nano-probes showed low cytotoxicity in the range of imaging concentration and did not affect cell proliferation. Successful preparation of nude mouse prostate cancer model. Fluorescence imaging system showed that the composite nano-probes were rapidly distributed in the major organs of nude mice and gradually concentrated in the tumor site; NMR showed that the nano-probes could clearly display the prostate cancer images within 24h; 4d after in vitro magnetic field irradiation, The growth of the probe in nude mice was significantly slower than that in the control nude mice (P <0.05). CONCLUSION: FMCNPs-ScFv can effectively target prostate cancer tissue and can be used in MRI of prostate cancer. It can also be used for tumor therapy under the action of magnetic field in vitro.