Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy.
Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy.
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DOI：
10.7150/thno.22621
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发表时间：
2018
期刊：
影响因子：
12.4
通讯作者：
Badea CT
中科院分区：
文献类型：
--
作者：
Ashton JR;Castle KD;Qi Y;Kirsch DG;West JL;Badea CT
金纳米粒子（AuNPs）正在成为癌症治疗和计算机断层扫描（CT）成像的有前途的药物。AuNP吸收X射线，随后在外部束放射治疗（RT）期间释放低能量、短程光电子，从而增加局部辐射剂量。当AuNP靠近肿瘤脉管系统时，额外的辐射剂量可导致血管通透性增加。这项工作的重点是了解肿瘤血管通透性如何受到AuNP增强RT的影响，以及这种影响如何用于改善纳米颗粒化疗药物的递送。研究方法：双能量CT用于定量在原发性软组织肉瘤的小鼠模型中在AuNP增强的RT之后脂质体碘和AuNP在肿瘤中的积累。将小鼠注射非靶向AuNPs、RGD-功能化AuNPs和非靶向AuNPs。（血管靶向），或没有AuNP，之后，它们接受不同剂量的RT治疗。小鼠注射脂质体碘或（用于成像研究）或脂质体阿霉素通过双能量CT（碘）或通过跟踪肿瘤治疗反应来评估增加的肿瘤脂质体积累（阿霉素）。结果如下：在20戈伊RT后观察到所有组的血管通透性显著增加，在10戈伊RT后观察到靶向和非靶向AuNP组的血管通透性显著增加，5戈伊RT后血管靶向金纳米颗粒组也是如此。靶向金纳米颗粒与5戈伊RT和脂质体阿霉素联合使用导致显著的肿瘤生长延迟与AuNP增强的RT或单独的化疗（肿瘤倍增时间~3-4天）相比，AuNP增强的RT或单独的化疗（肿瘤倍增时间~ 8天）具有更高的肿瘤倍增时间（肿瘤倍增时间~ 8天）。结论：血管靶向AuNP的添加显著改善了RT后脂质体阿霉素的治疗效果，这与成像研究中在肿瘤中观察到的脂质体积累增加一致。使用这种方法与脂质体药物递送系统可以增加化疗药物的特异性肿瘤递送，这有可能显着改善肿瘤反应并减少RT和化疗的副作用。
Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and computed tomography (CT) imaging. AuNPs absorb x-rays and subsequently release low-energy, short-range photoelectrons during external beam radiation therapy (RT), increasing the local radiation dose. When AuNPs are near tumor vasculature, the additional radiation dose can lead to increased vascular permeability. This work focuses on understanding how tumor vascular permeability is influenced by AuNP-augmented RT, and how this effect can be used to improve the delivery of nanoparticle chemotherapeutics. Methods: Dual-energy CT was used to quantify the accumulation of both liposomal iodine and AuNPs in tumors following AuNP-augmented RT in a mouse model of primary soft tissue sarcoma. Mice were injected with non-targeted AuNPs, RGD-functionalized AuNPs (vascular targeting), or no AuNPs, after which they were treated with varying doses of RT. The mice were injected with either liposomal iodine (for the imaging study) or liposomal doxorubicin (for the treatment study) 24 hours after RT. Increased tumor liposome accumulation was assessed by dual-energy CT (iodine) or by tracking tumor treatment response (doxorubicin). Results: A significant increase in vascular permeability was observed for all groups after 20 Gy RT, for the targeted and non-targeted AuNP groups after 10 Gy RT, and for the vascular-targeted AuNP group after 5 Gy RT. Combining targeted AuNPs with 5 Gy RT and liposomal doxorubicin led to a significant tumor growth delay (tumor doubling time ~ 8 days) compared to AuNP-augmented RT or chemotherapy alone (tumor doubling time ~3-4 days). Conclusions: The addition of vascular-targeted AuNPs significantly improved the treatment effect of liposomal doxorubicin after RT, consistent with the increased liposome accumulation observed in tumors in the imaging study. Using this approach with a liposomal drug delivery system can increase specific tumor delivery of chemotherapeutics, which has the potential to significantly improve tumor response and reduce the side effects of both RT and chemotherapy.