State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Biomaterials. 2012 Nov;33(33):8704-13. doi: 10.1016/j.biomaterials.2012.08.029. Epub 2012 Aug 29.
In this study, we report an anticancer drug delivery system based on doxorubicin (DOX)-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles. The as-synthesized nanoparticles consist of uniform spherical nanoparticles with an average diameter of 25 nm. The drug delivery system demonstrates the ability to release DOX by cleavage of the hydrazone bond in mildly acidic environments. The spectra overlap between emission of donor NaYF(4):Yb(3+)/Tm(3+) nanoparticles at 452 nm ((1)D(2)→(3)F(4)) and 477 nm ((1)G(4)→(3)H(6)) and the broad absorbance of acceptor DOX centered at around 480 nm enables energy transfer to occur between the nanoparticles and DOX. The quenching and recovery of the up-conversion luminescence of NaYF(4):Yb(3+)/Tm(3+) by DOX due to luminescence resonance energy transfer (LRET) mechanism are applied as optical probe to confirm the DOX conjunction and monitor the release of DOX. The DOX-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles exhibit an obvious cytotoxic effect on SKOV3 ovarian cancer cells via MTT assay. Meanwhile, the endocytosis process of DOX-conjugated NaYF(4):Yb(3+)/Tm(3+) nanoparticles by SKVO3 cells was demonstrated through confocal laser scanning microscopy (CLSM), flow cytometry and ICP-OES. Such drug delivery system, which combines pH-triggered drug-release and up-converting nanoparticles-based LRET property, has excellent potential applications in cancer therapy and smart imaging.
在这项研究中,我们报告了一种基于阿霉素(DOX)偶联 NaYF(4):Yb(3+)/Tm(3+)纳米粒子的抗癌药物输送系统。所合成的纳米粒子由平均直径为 25nm 的均匀球形纳米粒子组成。该药物输送系统在温和酸性环境中通过肼键的裂解表现出释放 DOX 的能力。供体 NaYF(4):Yb(3+)/Tm(3+)纳米粒子在 452nm((1)D(2)→(3)F(4))和 477nm((1)G(4)→(3)H(6))处的发射光谱与受体 DOX 的宽吸收光谱重叠,DOX 的中心在 480nm 左右,这使得能量能够在纳米粒子和 DOX 之间转移。由于发光共振能量转移(LRET)机制,DOX 对 NaYF(4):Yb(3+)/Tm(3+)上转换发光的猝灭和恢复被应用为光学探针来确认 DOX 的结合并监测 DOX 的释放。通过 MTT 测定法,DOX 偶联的 NaYF(4):Yb(3+)/Tm(3+)纳米粒子对 SKOV3 卵巢癌细胞表现出明显的细胞毒性作用。同时,通过共聚焦激光扫描显微镜(CLSM)、流式细胞术和 ICP-OES 证明了 DOX 偶联的 NaYF(4):Yb(3+)/Tm(3+)纳米粒子被 SKVO3 细胞内吞的过程。这种药物输送系统结合了 pH 触发的药物释放和上转换纳米粒子基 LRET 特性,在癌症治疗和智能成像方面具有极好的应用潜力。