Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.
Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.
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DOI：
10.1371/journal.pone.0034463
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Medina-Kauwe LK
中科院分区：
文献类型：
--
作者：
Hwang JY;Park J;Kang BJ;Lubow DJ;Chu D;Farkas DL;Shung KK;Medina-Kauwe LK
这项研究提出了一种新的多模式成像方法，包括高频超声，荧光强度，共聚焦和光谱成像，以改善体内新疗法的临床前评价。在这里，我们使用这种方法来评估体内的治疗效果的新的化疗结构，HerDox治疗期间和之后。HerDox由多柔比星非共价组装在靶向HER 2+肿瘤细胞的病毒样颗粒中组成，与非靶向药物相比，以低10倍以上的剂量引起肿瘤细胞死亡，同时保留心脏。虽然我们对HerDox的初步原理验证研究使用肿瘤生长/收缩率作为治疗效果的衡量标准，但在这里，我们表明在治疗期间和治疗后部署的多模式成像可以补充传统的肿瘤监测模式，以进一步表征治疗小鼠组织中的颗粒。具体来说，我们在这里表明，肿瘤细胞凋亡引起的HerDox可以在体内监测治疗过程中使用高频超声成像，而在原位共聚焦成像切除肿瘤显示，HerDox确实渗透肿瘤组织，并可以在亚细胞水平上检测到，包括在细胞核中，通过Dox荧光。此外，同一肿瘤组织的比率光谱成像能够定量区分HerDox荧光与原位自发荧光。与临床前评估的标准方法相比，这种新方法提供了多种/互补的信息，可以缩短体内疗效初步评估所需的时间，从而可能减少将新药分子转化为临床所需的时间和成本。
This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic.
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影响因子：
3.8
作者：
Vlad, Roxana M.;Kolios, Michael C.;Brock, Kristy K.
通讯作者：
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作者：
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作者：
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作者：
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通讯作者：
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20.1
作者：
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通讯作者：
Weissleder, R