Laboratory of Chemical Biology, State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
Department of Radiation Oncology, First Affiliated Hospital, Jilin University, 71 Xinmin Street, Changchun 130021, China.
Biomaterials. 2017 Sep;139:151-162. doi: 10.1016/j.biomaterials.2017.06.008. Epub 2017 Jun 6.
Most chemotherapeutic drugs commonly suffer from several shortcomings, including the lack of aqueous solubility, limited stability and adverse side effects. Although caging strategy has recently been employed as an effective approach to conceal and stabilize these drugs to achieve light-activated cancer therapy, it is plagued by the sophisticated drug modification process and deleterious solvent usage. In addition, using UV or Visible light to remove photocaged group is restricted to its limited tissue penetration ability in and phototoxicity. In this paper, by anchoring photochromic spiropyran on the mesoporous silica coated upconversion nanoparticles (UCNP-SP), we design a NIR-controlled cage mimicking system. Our results indicate that hydrophobic drug can be concealed inside the channels of the nanocarrier with high stability and "uncaged" via NIR irradiation-triggered hydrophobicity-hydrophilicity switch of the spiropyran molecules, finally inducing drug release and recovering their bioactivity. Moreover, under NIR illumination, the UV/Visible emissions from UCNP can also efficaciously initiate the generation of reactive oxygen species (ROS) by Curcumin, further improving the therapeutic efficiency. Both in vitro and in vivo experimental results validate that NIR irradiated nanosystem can produce remarkably enhanced antitumor efficiency.
大多数化疗药物通常存在几个缺点，包括缺乏水溶性、稳定性有限和副作用大。虽然笼状策略最近被用作一种有效的方法来隐藏和稳定这些药物，以实现光激活癌症治疗，但它受到复杂的药物修饰过程和有害溶剂使用的困扰。此外，使用 UV 或可见光去除光笼基团受到其在体内有限的组织穿透能力和光毒性的限制。在本文中，通过将光致变色螺吡喃锚定在介孔二氧化硅包覆的上转换纳米粒子（UCNP-SP）上，我们设计了一种近红外控制的模拟笼系统。我们的结果表明，疏水性药物可以通过近红外辐射触发螺吡喃分子的疏水性-亲水性转换，稳定地隐藏在纳米载体的通道内，并“解笼”，最终诱导药物释放并恢复其生物活性。此外，在近红外照射下，UCNP 的紫外/可见发射也可以有效地通过姜黄素引发活性氧（ROS）的产生，进一步提高治疗效率。体外和体内实验结果验证了近红外照射纳米系统可以产生显著增强的抗肿瘤效率。
