Affiliated Tumor Hospital of Guangxi Medical University , 71 He-di Road, Nanning 530021, People's Republic of China.
Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Tongji University School of Medicine , 301 Yan-chang-zhong Road, Shanghai 200072, People's Republic of China.
ACS Nano. 2017 Dec 26;11(12):12849-12862. doi: 10.1021/acsnano.7b08225. Epub 2017 Dec 15.
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.
缺氧作为实体肿瘤的一个特征标志，已被证明参与癌症转移和进展，诱导对氧依赖治疗的严重耐药，并阻碍治疗剂的输送。为了解决这些问题，建立了一种涉及改性氟碳（FC）链介导的氧输送方案的自供氧声动力学治疗（SDT）纳米平台，以实现高效的缺氧胰腺癌 SDT。在该纳米平台中，FC 链功能化的中空介孔有机硅纳米载体的介孔和 FC 链可以分别为声敏剂（IR780）和氧气提供足够的储存容量和结合位点。体外和体内实验表明，该纳米平台确实打破了缺氧特异性运输障碍，在超声辐射暴露下向缺氧 PANC-1 细胞提供足够的氧气，并缓解缺氧。因此，抑制了缺氧诱导的 SDT 耐药性，并产生了足够的高活性氧（ROS）来杀死 PANC-1 细胞并缩小缺氧 PANC-1 胰腺癌。这种独特的 FC 链介导的氧输送方法为缺氧供氧提供了一种途径，并在减轻缺氧诱导的对那些缺氧治疗的耐药性方面具有巨大的潜力，例如光动力疗法、放射疗法和化学疗法。
