Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China.
Angew Chem Int Ed Engl. 2021 Mar 8;60(11):5739-5743. doi: 10.1002/anie.202014833. Epub 2021 Feb 1.
The ability to accurately control the subcellular distribution of nanomedicines provides unique advantages on understanding of cellular biology and disease theranostics. The nanomedicine concentration is a key factor to affect the theranostic efficiency and systematic toxicity. Herein, we unravel a concentration-dependent subcellular distribution of near-infrared-emitting gold nanoparticles (AuNPs) co-coated with glutathione and a cell-penetrating peptide CR (CR-AuNPs), which shows a strong membrane-binding at high concentration but more endocytosis for mitochondria targeting at the low concentration region. Attributing to high content of Au and microsecond luminescent lifetimes, these AuNPs can catalyze dissolved oxygen to generate singlet oxygen ( O ) efficiently. Combining with the concentration-dependent subcellular distribution, the luminescent AuNPs show photocytotoxicity in the relative low concentration region. These findings facilitate the fundamental understanding of the biological behaviors and potential cytotoxicity of ultrasmall luminescent AuNPs toward future theranostics.
准确控制纳米药物的亚细胞分布为理解细胞生物学和疾病治疗提供了独特的优势。纳米药物浓度是影响治疗效果和系统毒性的关键因素。在此，我们揭示了近红外发光金纳米粒子（AuNPs）与谷胱甘肽和穿透肽 CR 共包覆的浓度依赖性亚细胞分布，其在高浓度下显示出强烈的膜结合，但在低浓度区域更多地内吞作用以靶向线粒体。由于 Au 的高含量和微秒级的发光寿命，这些 AuNPs 可以有效地将溶解氧催化生成单线态氧（1O2）。结合浓度依赖性的亚细胞分布，发光 AuNPs 在相对低浓度区域表现出光细胞毒性。这些发现有助于深入了解超小发光 AuNPs 的生物学行为和潜在细胞毒性，为未来的治疗提供了依据。
