A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways.
A photoactivable multi-inhibitor nanoliposome for tumour control and simultaneous inhibition of treatment escape pathways.
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DOI：
10.1038/nnano.2015.311
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发表时间：
2016-04
影响因子：
38.3
通讯作者：
Hasan T
中科院分区：
文献类型：
--
作者：
Spring BQ;Bryan Sears R;Zheng LZ;Mai Z;Watanabe R;Sherwood ME;Schoenfeld DA;Pogue BW;Pereira SP;Villa E;Hasan T
纳米级药物输送载体可以通过促进肿瘤选择性药物释放来促进癌症的多模式治疗。然而，很少有有效的方法，因为癌细胞发展出抵抗和逃避治疗的方法。在这里，我们介绍了一种可光激活的多抑制物纳米脂质体(PMIL)，它在光引发和持续释放抑制肿瘤再生和治疗逃逸信号通路的同时提供光诱导的细胞毒性。PMIL包括一个在脂质双层中掺杂了可光激活的发色团(苯并卟啉衍生物，BPD)的纳米脂质体，以及一个包裹在其中的纳米颗粒，其中包含一种多激酶抑制剂卡波赞替尼(XL184)。静脉注射PMIL后的近红外肿瘤照射，触发肿瘤细胞和微血管的光动力学损伤，同时启动XL184在肿瘤内的释放。单一的PMIL治疗在两个小鼠模型中实现了肿瘤的长期减少，并抑制了原位胰腺肿瘤模型中的转移逃逸。PMIL通过实现药物释放的时空控制，同时减少全身药物暴露和相关毒性，为癌症治疗提供了新的前景。
Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivatable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with photo-initiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivatable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)—a multikinase inhibitor—encapsulated inside. Near infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release whilst reducing systemic drug exposure and associated toxicities.