Multifunctional theranostic contrast agent for photoacoustics- and ultrasound-based tumor diagnosis and ultrasound-stimulated local tumor therapy
Multifunctional theranostic contrast agent for photoacoustics- and ultrasound-based tumor diagnosis and ultrasound-stimulated local tumor therapy
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DOI：
10.1016/j.jconrel.2015.09.060
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发表时间：
2015-11-28
影响因子：
10.8
通讯作者：
Kim, Hyuncheol
中科院分区：
文献类型：
--
作者：
Moon, Hyungwon;Kang, Jeeun;Kim, Hyuncheol
生物医学影像引导下的肿瘤治疗应具备准确的肿瘤诊断能力和高疗效的个性化治疗能力。目前正在研究各种生物医学成像引导的癌症治疗，以克服目前的局限性，包括诊断灵敏度低和药物输送到肿瘤部位差。在这里，我们报告了一种多功能治疗诊断造影剂的发展，展示了高灵敏度的光声和超声成像和有效的局部抗癌药物输送到肿瘤部位。利用磷脂-卟啉偶联物制备了一种可同时增强超声和光声信号的微泡（卟啉-MB）。然后将紫杉醇负载的人血清白蛋白纳米粒（PTX-HSA-NPs）缀合到微泡的表面上。开发的PTX-HSA-NPs缀合的卟啉-MB（卟啉-MB-NPs）在用于光声成像的700 nm最佳激光波长和用于超声成像的5-14 MHz工作频率下提供了肿瘤的灵敏的双模图像。此外，卟啉-MB-NPs通过超声暴露有效地抑制肿瘤生长。暴露于聚焦超声引发卟啉-MB-NPs的塌陷，导致PTX-HSA-NPs的局部释放并增强对肿瘤部位的渗透。PTX-HSA-NPs的增加的优先积累和渗透抑制肿瘤生长比没有暴露于超声的情况多10倍。总之，所开发的卟啉-MB-NPs在同时双功能超声/光声成像诊断和纳米药物的局部触发释放以及增强的化疗效率方面建立了新的范例。(C)2015 Elsevier B. V.版权所有。
Biomedical imaging-guided cancer therapy should have capabilities of both accurate tumor diagnosis and high therapeutic efficacy for the personalized treatment. Various biomedical imaging-guided cancer therapies are currently being investigated to overcome current limitations that include low sensitivity of diagnosis and poor drug delivery to the tumor site. Here, we report the development of a multifunctional theranostic contrast agent demonstrating high sensitive photoacoustic and ultrasound imaging and effective local delivery of anticancer drug to a tumor site. A microbubble (porphyrin-MB) was developed using phospholipid-porphyrin conjugates to enhance ultrasound and photoacoustic signal intensities simultaneously. Paclitaxel-loaded human serum albumin nanoparticles (PTX-HSA-NPs) were then conjugated onto the surface of the microbubble. The developed PTX-HSA-NPs conjugated porphyrin-MB (porphyrin-MB-NPs) provided sensitive, dual modal images of a tumor at 700 nm optimal laser wavelength for photoacoustic imaging and 5-14 MHz operating frequency for the ultrasound imaging. In addition, porphyrin-MB-NPs efficiently suppressed tumor growth by ultrasound exposure. Exposure to the focused ultrasound triggered the collapse of porphyrin-MB-NPs, resulting in the local release of PTX-HSA-NPs and enhanced penetration into the tumor site. The increased preferential accumulation and penetration of PTX-HSA-NPs suppressed tumor growth 10-fold more than without exposure to ultrasound. In conclusion, the developed porphyrin-MB-NPs establish a new paradigm in simultaneous bi-functional ultrasound/photoacoustic imaging diagnosis and locally triggered release of nanomedicine and enhanced chemotherapy efficiency. (C) 2015 Elsevier B.V. All rights reserved.