诊疗一体多孔磁性微球用于增加乳腺癌中央区域显像引导下的精准药物递送

The convection and the diffusion of the drug at the center of the tumor is the main challenge that we encountered. Aiming at this problem, our team tailored a novel porous magnetic microsphere with the potential ability in enhancing photoacoustic/magnetic resonance imaging, encapsulating drug and responding to ultrasound. Luckily, we found that these microspheres can deposit at the intratumoral vessels and embolize these vessels, and without vascular embolization at the normal tissue after the intravenous injection. We inferred that the reason why the microspheres can specifically deposit at the tumor vessels is the dramatical discrepancy of vascular structure and hemodynamic between the tumor vessels and the normal vessels. Herein, this project proposed that using the dynamic contrast-enhanced magnetic resonance imaging and multi-photon laser scanning microscopic imaging techniques investigate the doxorubicin-loaded microspheres’ delivery in MDA-MB-231 tumor-bearing nude mice and the dorsal skinfold window chamber model of the MDA-MB-231 tumor-bearing nude mice in order to ascertain the mechanism of these microspheres inducing the intratumoral vessels’ embolization, and to elucidate that mechanism of the increased drug convection/diffusion via doxorubicin-loaded microspheres embolizing the intratumoral vessels. Furthermore, it might propose an alternative strategy for imaging-guided precise drug delivery.

化疗药物在肿瘤中央区的交换/弥散是目前化疗治疗肿瘤所面临的主要问题。针对这一问题，本团队前期围绕药物递送已研发出具有光声/磁共振双模态显像、载药及声响应潜能的多孔磁性微球，该微球经静脉注射后可栓塞肿瘤中央区血管，而正常组织血管未见栓塞。此现象的产生我们推测是由肿瘤中央区血管与正常血管结构及血流动力学差异所导致。因此，本项目拟采用动态增强磁共振成像及多光子激光扫描显微成像技术分别研究载阿霉素多孔磁性微球在乳腺癌MDA-MB-231的普通荷瘤裸鼠模型及载背脊皮翼窗荷瘤裸鼠模型中的递送，旨在从影像学显像及活体微观显像层面来探索该微球特异性栓塞肿瘤血管的机制，阐明载阿霉素多孔磁性微球栓塞肿瘤血管后所致药物交换/弥散增加的机理，进一步为显像引导下的精准药物递送提供一种新的策略。

化疗药物在肿瘤中央区的交换/弥散是目前化疗治疗肿瘤所面临的主要问题。针对这一问题，本团队围绕药物递送，研发出具有光声/磁共振双模态显像、载药及声响应的多孔磁性微球，该微球经静脉注射后可栓塞肿瘤中央区血管，而正常组织血管未见栓塞。同时，为实现活体中肿瘤血管栓塞的实时监控，研究期间成功构建的背脊皮窗模型及超分辨血管实时显像技术的应用研发对肿瘤微循环及药物代谢情况实现了微观层面的实时观测，并对其在各脏器的药物代谢及分布情况作出了初步探索。为进一步为显像引导下的精准药物递送提供一种新的策略。

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