Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy
Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy
复制标题
金属卟啉封装的可生物降解纳米系统用于高效磁共振成像引导声动力癌症治疗
DOI：
10.1021/jacs.6b11846
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发表时间：
2017-01-25
影响因子：
15
通讯作者：
Shi, Jianlin
中科院分区：
文献类型：
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作者：
Huang, Ping;Qian, Xiaoqin;Shi, Jianlin
传统的光动力疗法（PDT）存在光穿透组织深度低和潜在的光毒性的关键问题，这些问题有望通过开发基于动态疗法的新型治疗方式如声动力疗法（SDT）来解决。在这项工作中，我们报道了一种高性能多功能纳米粒子声敏剂的设计/制造，用于有效的体内磁共振成像（MRI）引导的SDT抗癌。所开发的方法利用介孔有机硅纳米系统的结构和组成特征来制造具有有趣治疗性能的声敏剂。明确定义的介孔有利于高负载有机声敏剂（原卟啉，PpIX）和基于金属卟啉化学（MnPpIX）的顺磁性过渡金属Mn离子的进一步螯合。大表面积的介孔结构也最大限度地提高了水分子对包裹顺磁性Mn离子的可及性，使复合声敏剂具有显著的高MRI性能(r(1) = 9.43 mM(-1) s(-2))，可用于SDT引导和监测。重要的是，所开发的多功能声敏剂（HMONs-MnPpIX-PEG）具有可控的生物降解行为和高生物相容性，在体外诱导癌细胞死亡和体内抑制肿瘤生长方面表现出独特的高SDT效率。本报告提供了一个范例，即基于精心设计的高性能多功能声敏剂的纳米技术增强SDT将充分利用超声治疗的优点（无创、方便、经济等），为快速发展的纳米医学为高效治疗癌症铺平新的道路。
Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic Mn ions, endowing the composite sonosensitizers with markedly high MRI performance (r(1) = 9.43 mM(-1) s(-2)) for SDT guidance and monitoring. Importantly, the developed multifunctional sonosensitizers (HMONs-MnPpIX-PEG) with controllable biodegradation behavior and high biocompatibility show distinctively high SDT efficiency for inducing the cancer-cell death in vitro and suppressing the tumor growth in vivo. This report provides a paradigm that nanotechnology-enhanced SDT based on elaborately designed high-performance multifunctional sonosensitizers will pave a new way for efficient cancer treatment by fully taking the advantages (noninvasiveness, convenience, cost-effectiveness, etc.) of ultrasound therapy and quickly developing nanomedicine.