Oxygen-Self-Produced Nanoplatform for Relieving Hypoxia and Breaking Resistance to Sonodynamic Treatment of Pancreatic Cancer
Oxygen-Self-Produced Nanoplatform for Relieving Hypoxia and Breaking Resistance to Sonodynamic Treatment of Pancreatic Cancer
复制标题
自产氧纳米平台缓解缺氧、打破胰腺癌声动力治疗耐药
DOI：
10.1021/acsnano.7b08225
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发表时间：
2017-12-01
期刊：
影响因子：
17.1
通讯作者：
Liu, Junjie
中科院分区：
文献类型：
--
作者：
Chen, Jie;Luo, Honglin;Liu, Junjie
低氧作为实体瘤的一个特征性标志，已被证明参与癌症转移和进展，诱导对氧依赖性治疗的严重抵抗，并阻碍治疗诊断剂的运输。为了解决这些问题，已经建立了一种涉及经修改的氟碳（FC）链介导的氧递送方案的氧气自产生声动力学疗法（SDT）纳米平台，以实现针对缺氧胰腺癌的高效SDT。在该纳米平台中，FC链官能化的中空介孔有机二氧化硅纳米颗粒载体的介孔和FC链可以分别为声敏剂（IR 780）和氧提供足够的存储容量和结合位点。体外和体内实验表明，涉及这种独特的氧气输送方案的纳米平台确实打破了缺氧特异性运输屏障，为缺氧的PANC-1细胞提供足够的氧气，特别是在暴露于超声辐射时，并缓解缺氧。因此，缺氧诱导的对SDT的抗性被抑制，并产生足够的高活性氧（ROS）来杀死PANC-1细胞并缩小缺氧的PANC-1胰腺癌。这种独特的FC链介导的氧递送方法提供了缺氧氧合的途径，并且在减轻缺氧诱导的对那些氧耗尽疗法的抗性方面具有巨大潜力，例如，光动力疗法、放射疗法和化学疗法。
Hypoxia as one characteristic hallmark of solid tumors has been demonstrated to be involved in cancer metastasis and progression, induce severe resistance to oxygen-dependent therapies, and hamper the transportation of theranostic agents. To address these issues, an oxygen-self-produced sonodynamic therapy (SDT) nanoplatform involving a modified fluorocarbon (FC)-chain-mediated oxygen delivery protocol has been established to realize highly efficient SDT against hypoxic pancreatic cancer. In this nanoplatform, mesopores and FC chains of FC-chain-functionalized hollow mesoporous organosilica nanoparticle carriers can provide sufficient storage capacity and binding sites for sonosensitizers (IR780) and oxygen, respectively. In vitro and in vivo experiments demonstrate the nanoplatform involving this distinctive oxygen delivery protocol indeed breaks the hypoxia-specific transportation barriers, supplies sufficient oxygen to hypoxic PANC-1 cells especially upon exposure to ultrasound irradiation, and relieves hypoxia. Consequently, hypoxia-induced resistance to SDT is inhibited and sufficient highly reactive oxygen species (ROS) are produced to kill PANC-1 cells and shrink hypoxic PANC-1 pancreatic cancer. This distinctive FC-chain-mediated oxygen delivery method provides an avenue to hypoxia oxygenation and holds great potential in mitigating hypoxia-induced resistance to those oxygen depleted therapies, e.g., photodynamic therapy, radiotherapy, and chemotherapy.