Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.
Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.
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DOI：
10.1371/journal.pone.0062425
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dorsey JF
中科院分区：
文献类型：
--
作者：
Joh DY;Sun L;Stangl M;Al Zaki A;Murty S;Santoiemma PP;Davis JJ;Baumann BC;Alonso-Basanta M;Bhang D;Kao GD;Tsourkas A;Dorsey JF
脑肿瘤（如多形性胶质母细胞瘤（GBM））的成功治疗在很大程度上受到可以安全给予的放射治疗（RT）累积剂量和血脑屏障（BBB）的限制，血脑屏障限制了全身性抗癌药物向肿瘤组织的递送。因此，总的前景仍然严峻。在此，我们报告了我们在细胞培养实验和GBM动物模型中的初步研究，其中RT是由PEG化金纳米颗粒（GNP）补充的。GNP显著增加了电离辐射对人GBM衍生细胞系造成的细胞DNA损伤，并导致克隆形成存活率降低（剂量增强比为1.3）。有趣的是，GNP和RT的组合也导致脑血管DNA损伤显着增加。后续体外实验证实，GNP和RT的组合导致脑源性内皮细胞中DNA损伤显著增加。最后，GNP和RT的组合增加了具有原位GBM肿瘤的小鼠的存活率。先前对患有脑肿瘤的小鼠的治疗导致GNP的外渗和肿瘤内沉积增加，这表明可以利用RT诱导的BBB破坏来改善GNP的肿瘤组织靶向，从而进一步优化GNP对脑肿瘤的放射增敏作用。这些令人兴奋的结果共同表明，GNP可以有效地整合到脑肿瘤的RT治疗中，具有潜在的益处，这是由于肿瘤细胞对肿瘤相关血管系统的优先靶向的放射增敏性增加。
Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.
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体内模型系统中TNF-α涂层金纳米颗粒的生物分布。
DOI：
10.2217/nnm.09.21
发表时间：
2009-06
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Goel R;Shah N;Visaria R;Paciotti GF;Bischof JC
通讯作者：
Bischof JC
多功能纳米颗粒作为耦合对比剂。
影响因子：
16.6
作者：
Jin, Yongdong;Jia, Congxian;Huang, Sheng-Wen;O'Donnell, Matthew;Gao, Xiaohu
通讯作者：
Gao, Xiaohu
影响因子：
--
作者：
Baumann, Brian C.;Kao, Gary D.;Dorsey, Jay F.
通讯作者：
Dorsey, Jay F.
DOI：
10.1007/s10967-007-0230-1
发表时间：
2007-02-01
影响因子：
1.6
作者：
James, W. D.;Hirsch, L. R.;Payne, J. D.
通讯作者：
Payne, J. D.
影响因子：
4.9
作者：
Chattopadhyay, Niladri;Cai, Zhongli;Reilly, Raymond M.
通讯作者：
Reilly, Raymond M.