Wu Xuan, Wang Le, Xu Yan-Neng, Chen Jian-Li, Luo Kathy Qian, Yuan Ming-Heng, Li Jie, Yuan Gang, Gu Ze-Yun, Jia Xiao-Hui, Chen Xiuping, Zhu Xiao-Ming, Jiang Ruibin
State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau S.A.R., 999078, China.
Shaanxi Key Laboratory for Advanced Energy Devices, Shaanxi Engineering Lab for Advanced Energy Technology, School of Materials Science and Engineering, Shaanxi Normal University, Xi'an, 710119, China.
Small. 2022 Jul;18(29):e2200522. doi: 10.1002/smll.202200522. Epub 2022 Jun 24.
The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.
用于癌症治疗的纳米药物设计，尤其是肿瘤转移的治疗，已受到广泛关注。蛋白酶体抑制被认为是一种新的癌症治疗策略。尽管作为蛋白酶体抑制剂的卡非佐米（CFZ）在多发性骨髓瘤治疗方面取得了重大突破，但对于实体瘤和转移瘤治疗仍不尽人意。在本研究中，合成了中空氮化钛（TiN）纳米壳作为CFZ的药物载体。TiN纳米壳对CFZ具有高负载能力，其对自噬的内在抑制作用协同增强了CFZ的活性。由于在第二近红外（NIR-II）区域具有优异的光热转换效率，基于TiN纳米壳的光热疗法进一步诱导了协同抗癌效果。体内研究表明，TiN纳米壳很容易引流到负责肿瘤淋巴转移的淋巴结中。负载CFZ的基于TiN纳米壳的化学-光热疗法联合手术在极大抑制癌细胞进一步转移扩散方面提供了显著的治疗效果。这些发现表明，TiN纳米壳作为CFZ的有效载体，可实现基于蛋白酶体抑制剂的癌症治疗的增强效果，并且这项工作还提出了一种“化学-光疗辅助手术”策略，有望用于未来的癌症治疗。
