SPECT-CT引导体外控释多功能金纳米胶囊治疗晚期前列腺癌的实验研究

Prostate cancer is a common malignant tumor of male reproductive system. It is still one of the most important research areas to explore effective treatment for advanced androgen-independent prostatic cancer, slow down the tumor progression and expand the life. Gold nanocapsules are constructed with loading Taxotere and Na[99mTcO4] into the core hollow space. On the surface of gold nanocapsules, Folid acid is conjugated for targeting, and PEG is designed for protecting gold nanoparticles from the rapid clearance of reticuloendothelial system. SPECT-CT provides optical guidance in nude mice bearing human prostate cancer xenograft, and gold nanocapsule absorbs near-infrared light strongly to generate heat and then may offer a targeted ablative treatment and chemotherapy for prostate cancer. It is hopeful to improve the prognosis of advanced androgen-independent prostatic cancer. And it is also helpful for the targeted treatment of other refractory tumors.

前列腺癌是男性生殖系统常见的恶性肿瘤。探索针对晚期非激素依赖性前列腺癌的新型有效的治疗策略，延缓肿瘤进展时间，延长前列腺癌患者的总生存时间，一直是前列腺癌研究的重点。本研究拟构建内径可调的多功能金纳米胶囊，内载化疗药物Taxotere和核素99mTc，表面装备叶酸，并辅以PEG修饰，使其既能载药靶向前列腺癌组织，又能逃避机体防御系统的清除。SPECT-CT显像荷人前列腺癌裸鼠，立体定位引导体外近红外线定向照射，受照金纳米胶囊解体，释放Taxotere于前列腺癌组织局部，实施前列腺癌体外控释靶向化疗+热消融联合治疗。以期改善晚期非激素依赖性前列腺癌的预后，并为其他难治性肿瘤的靶向治疗提供了新策略。

背景：研制多功能金纳米微球体外控释载药体，探讨其对晚期前列腺癌裸鼠模型的治疗功效。.主要研究内容：金纳米空心微球HGNs表面进行PEG修饰，组装叶酸和99mTc螯合剂，形成多功能金纳米空心微球MGNs。99mTc标记MGNs（99mTc-MGNs），流式细胞仪测试对PC-3细胞凋亡的影响，体外结合试验检测与PC-3细胞结合特异性。荷瘤裸鼠体尾静脉注射99mTc-MGNs进行体内分布研究。然后MGNs运载Docetaxel （MGN@DTX），测算DTX包载量及体外近红外线照射下DTX释放率，并检测分析MGN@DTX血清稳定性和PC-3细胞毒性作用。最后，评价MGN@DTX在荷前列腺癌PC-3裸鼠中的抗癌效能。.结果：快速薄层层析法获99mTc-MGN标记率为97.69%。MGN能特异性结合PC-3细胞，且在体外受过量叶酸抑制。MGN@DTX在体外血清中24h能保持较好稳定性；经红外线照射后，对PC-3细胞活性抑制作用高于DTX组。荷前列腺癌PC-3裸鼠接受治疗后第28天，MGN@DTX + NIR laser组裸鼠肿瘤抑制率明显高于DTX组和MGNs + NIR laser组。.结论：MGNs运载化疗药物可增强抗肿瘤化疗功效，减少正常组织细胞损害和机体化疗耐药。该项研究为晚期前列腺癌的治疗提供了一种有希望的治疗策略。