Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer
Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer
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使用负载多西紫杉醇的金纳米球进行有效光热化疗治疗晚期前列腺癌
DOI：
10.3109/1061186x.2015.1018910
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发表时间：
2015-07
影响因子：
4.5
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Dong QJ;Hu QR;Bai LY;Chen J
摘要背景：制备负载多西他赛的多功能金纳米球（MGN@DTX），并在携带人前列腺癌异种移植物的裸鼠中评价其治疗功效。方法：以叶酸和DTPTT螯合物为载体，聚乙二醇修饰空心金纳米球（HGNs）制备MGNs。用流式细胞仪检测标记的MGNs对PC-3细胞凋亡的影响，用细胞结合实验检测标记MGNs与PC-3细胞的结合亲和力。接下来，通过SPECT成像测量99 mTc-MGN在异种移植荷瘤小鼠中的生物分布。此外，在MGN@DTX中估计DTX负载和释放速率。最后，评估了MGN@DTX在人血清中的体外稳定性和细胞毒性，以及它们在异种移植荷瘤小鼠中的抗肿瘤作用。结果：99 mTc-MGNs（纯度97.69%）与PC-3细胞表现出良好的结合亲和力，这种特异性识别被过量的叶酸阻断。有趣的是，MGN@DTX在人血清中保持稳定24小时，并且在NIR激光照射后表现出比游离DTX更高的平均细胞毒性。到第28天，MGN@DTX + NIR激光照射组的肿瘤抑制率高于DTX和MGN + NIR激光照射组。结论：将化疗药物负载到MGNs中可以增加抗肿瘤效力，减少正常细胞损伤并降低耐药性，从而代表晚期前列腺癌治疗的有希望的方法。
Abstract Background: Multifunctional gold nanospheres (MGNs)-loaded with docetaxel (MGN@DTX) were prepared and evaluated for therapeutic efficacy in nude mice bearing human prostate cancer xenografts. Methods: MGNs were prepared from PEGylated hollow gold nanospheres (HGNs) coated with folic acid and DTPTT chelate. Then, the effect of radiolabelled MGNs (99mTc-MGNs) on PC-3 cell apoptosis was assessed by flow cytometry, while their binding affinity to these cells was evaluated by cell binding assays. Next, biodistribution of 99mTc-MGNs in xenograft bearing mice was measured by SPECT imaging. Also, DTX loading and release rates were estimated in MGN@DTX. Finally, in vitro stability in human serum and cytotoxicity of MGN@DTX were assessed, as well as their antitumor effect in xenograft bearing mice. Results: 99mTc-MGNs (97.69% purity) showed good binding affinity to PC-3 cells, a specific recognition blocked by excess folic acid. Interestingly, MGN@DTX remained stable in human serum for 24 h, and exhibited higher mean cytotoxicity after NIR laser irradiation than free DTX. By day 28, tumor inhibition rates were higher in the MGN@DTX + NIR laser irradiation group compared with the DTX and MGNs + NIR laser irradiation groups. Conclusions: Loading chemotherapeutic drugs into MGNs can increase antitumor potency, reduce normal cell damage and decrease drug resistance, thus representing a promising approach for advanced prostate cancer treatment.
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影响因子：
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