Date Published: February 07, 2018
Publisher: John Wiley and Sons Inc.
Author(s): Donghui Wang, Naijian Ge, Tingting Yang, Feng Peng, Yuqin Qiao, Qianwen Li, Xuanyong Liu.
Construction of localized drug‐eluting systems with synergistic chemothermal tumor‐killing abilities is promising for biomedical implants directly contacting with tumor tissues. In this study, an intelligent and biocompatible drug‐loading platform, based on a gold nanorods‐modified butyrate‐inserted NiTi‐layered double hydroxides film (Au@LDH/B), is prepared on the surface of nitinol alloy. The prepared films function as drug‐loading “sponges,” which pump butyrate out under near‐infrared (NIR) irradiation and resorb drugs in water when the NIR laser is shut off. The stimuli‐responsive release of butyrate is verified to be related with the NIR‐triggered crystal phase transformation of Au@LDH/B. In vitro and in vivo studies reveal that the prepared films possess excellent biosafety and high efficiency in synergistic thermochemo tumor therapy, showing a promising application in the construction of localized stimuli‐responsive drug‐delivery systems.
With shape memory effect, superelasticity, and biocompatibility, nitinol has been widely used in biomedical applications,1, 2, 3 especially tumor‐contacting implants and medical devices. One of the most commercially successful examples of utilization of nitinol is the production of expandable stents, which are applied in the palliation treatment of malignant obstruction of trachea, brochi, esophagus, and bile duct.4, 5, 6, 7, 8 The occlusion can be caused by many kinds of cancers, such as gallbladder carcinoma, esophagus carcinoma, cholangiocarcinoma, gastric carcinoma, and so on. However, tumor ingrowth and overgrowth into the nitinol stents often causes reocclusion, leading to durability reduction and function degradation subsequently.9 Therefore, developing nitinol stents with antitumor abilities is highly desirable.
In summary, an intelligent localized drug‐loading film based on GNRs‐modified NiTi‐LDHs was designed for the synergistic chemothermal tumor therapy. The prepared film works like a “sponge,” it absorbs and stores drugs inside its crystal lattice, and pump drugs outside when the film is “squeezed” by NIR; when the NIR irradiation is stopped, the excess drugs in the environment can be reabsorbed by the drug‐loading “sponge,” endow the prepared films with high biocompatibility. The NIR‐controlled drug release is benefited from the phase transformation of NiTi‐LDHs. When Au@LDH/B exposes to NIR, the photothermal effect of GNRs increase the temperature of NiTi‐LDHs film, leading to its crystal phase change from layered double hydroxides to layered double oxides, butyrate ions stored interlayer release accordingly. In vitro and in vivo experiments verified Au@LDH/B samples present distinct synergistic effect in the chemothermal tumor therapy, which is promising to overcome the inevitable tumor recurrence and metastasis resulted from the inhomogeneous ablation of single thermal therapy. Therefore, the newly designed GNRs‐modified butyrate‐inserted NiTi‐LDHs films show great potential to be used in the surface modification of implants in contact with tumor tissues.
The authors declare no conflict of interest.