Yao Yong, Wang Yang, Zhao Ruibo, Shao Li, Tang Ruikang, Huang Feihe
State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.
J Mater Chem B. 2016 Apr 21;4(15):2691-2696. doi: 10.1039/c5tb02611c. Epub 2016 Apr 4.
In order to improve the effectiveness of cancer therapy and reduce the adverse effects of conventional chemotherapy, the development of less toxic, biocompatible, decomposable and pH-responsive nano-containers is of great importance. In this work a novel nano-container is designed and synthesized by doping a water-soluble pillar[5]arene WP5 onto hollow mesoporous silica nanoparticles (HMNPs) via host-guest complexation. This nano-container decomposes into small water-soluble fragments to achieve a highly efficient release of the loaded anticancer drug doxorubicin. Importantly, the complexation of WP5 molecules with HMNPs significantly improves the inhibition of tumor growth in vivo with minimal side effects, which can be attributed to the pH-responsiveness of the host-guest interactions. Under the extracelluar conditions, the host-guest complexation between WP5 and HMNPs enhances the loading of doxorubicin molecules. However, this host-guest complexation is prohibited under the low pH conditions in intracellular lysosomes, so that doxorubicin is released readily from the vector. The present novel drug delivery system demonstrates the great potential of host-guest complexation for cancer therapy improvement.
为了提高癌症治疗的有效性并减少传统化疗的副作用，开发毒性更低、生物相容性好、可分解且对pH响应的纳米容器具有重要意义。在这项工作中，通过主客体络合将水溶性柱[5]芳烃WP5掺杂到中空介孔二氧化硅纳米颗粒（HMNPs）上，设计并合成了一种新型纳米容器。这种纳米容器分解成小的水溶性片段，以实现负载的抗癌药物阿霉素的高效释放。重要的是，WP5分子与HMNPs的络合显著提高了体内对肿瘤生长的抑制作用，且副作用最小，这可归因于主客体相互作用的pH响应性。在细胞外条件下，WP5与HMNPs之间的主客体络合增强了阿霉素分子的负载。然而，在细胞内溶酶体的低pH条件下，这种主客体络合被禁止，从而使阿霉素易于从载体中释放出来。目前的新型药物递送系统展示了主客体络合在改善癌症治疗方面的巨大潜力。
