Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , 5625 Renmin Street, Changchun, Jilin 130022, China.
University of Chinese Academy of Sciences , Beijing 100049, China.
Nano Lett. 2018 Feb 14;18(2):886-897. doi: 10.1021/acs.nanolett.7b04162. Epub 2018 Jan 17.
Gold (Au) core@void@copper sulfide (CuS) shell (Au-CuS) yolk-shell nanoparticles (YSNPs) were prepared in the present study for potential chemo-, photothermal, and photodynamic combination therapy, so-called "chemophototherapy". The resonance energy transfer (RET) process was utilized in Au-CuS YSNPs to achieve both enhanced photothermal and photodynamic performance compared with those of CuS hollow nanoparticles (HNPs). A series of Au nanomaterials as cores that had different localized surface plasmon resonance (LSPR) absorption peaks at 520, 700, 808, 860, and 980 nm were embedded in CuS HNPs to screen the most effective Au-CuS YSNPs according to the RET process. Thermoresponsive polymer was fabricated on these YSNPs' surface to allow for controlled drug release. Au-CuS and Au-CuS YSNPs were found capable of inducing the largest temperature elevation and producing the most significant hydroxyl radicals under 808 and 980 nm laser irradiation, respectively, which could accordingly cause the most severe 4T1 cell injury through oxidative stress mechanism. Moreover, doxorubicin-loaded (Dox-loaded) P(NIPAM-co-AM)-coated Au-CuS (p-Au-CuS@Dox) YSNPs could more efficiently kill cells than unloaded particles upon 980 nm laser irradiation. After intravenous administration to 4T1 tumor-bearing mice, p-Au-CuS YSNPs could significantly accumulate in the tumor and effectively inhibit the tumor growth after 980 nm laser irradiation, and p-Au-CuS@Dox YSNPs could further potentiate the inhibition efficiency and exhibit excellent in vivo biocompatibility. Taken together, this study sheds light on the rational design of Au-CuS YSNPs to offer a promising candidate for chemophototherapy.
金（Au）核@空@硫化铜（CuS）壳（Au-CuS）蛋黄-壳纳米粒子（YSNPs）被制备用于潜在的化学-光热和光动力联合治疗，即“化学-光疗”。在 Au-CuS YSNPs 中利用共振能量转移（RET）过程，与 CuS 空心纳米粒子（HNPs）相比，实现了光热和光动力性能的增强。一系列金纳米材料作为核，在 520、700、808、860 和 980nm 处具有不同的局域表面等离子体共振（LSPR）吸收峰，被嵌入到 CuS HNPs 中，根据 RET 过程筛选出最有效的 Au-CuS YSNPs。在这些 YSNPs 的表面上制备了温敏聚合物，以允许控制药物释放。Au-CuS 和 Au-CuS YSNPs 分别在 808 和 980nm 激光照射下被发现能够引起最大的温度升高并产生最显著的羟基自由基，这可以通过氧化应激机制导致最严重的 4T1 细胞损伤。此外，负载阿霉素（Dox-loaded）的 P（NIPAM-co-AM）-包裹的 Au-CuS（p-Au-CuS@Dox）YSNPs 在 980nm 激光照射下比未负载的颗粒更有效地杀死细胞。静脉注射到 4T1 荷瘤小鼠后，p-Au-CuS YSNPs 可以在 980nm 激光照射后显著积聚在肿瘤中，并有效抑制肿瘤生长，p-Au-CuS@Dox YSNPs 可以进一步增强抑制效率并表现出优异的体内生物相容性。总之，这项研究为 Au-CuS YSNPs 的合理设计提供了启示，为化学-光疗提供了一种有前途的候选药物。
