Sprengel Carla, David Céline, Berning Lena, Nollmann Cathrin, Lenz Thomas, Stühler Kai, Stork Björn, Heinzel Thomas
Solid State Physics Laboratory, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, Germany.
Institute of Molecular Medicine I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, 40225 Düsseldorf, Germany.
iScience. 2024 Dec 25;28(1):111654. doi: 10.1016/j.isci.2024.111654. eCollection 2025 Jan 17.
We present functional studies of lysosomes in human cells after uptake of carbon nanodots (CNDs). Even under high CND concentrations, the lysosomal functionality, as characterized via cathepsins B and L as well as the autophagic markers SQSTM1/p62 and LC3B-II, is maintained. Furthermore, branched polyethylenimine (bPEI) molecules have been coupled to the CNDs as a model functionalization or example of a drug. We observe that the bPEI-CND conjugates accumulate to a higher degree in the lysosomes as compared to bPEI or CND alone. Here, changes in the lysosomal size and function are observed, which can be explained exclusively by the bPEI. It is concluded that CNDs are highly efficient and inert carriers for functional molecules into lysosomes as target, with the added value that lysosomal escape is suppressed, thereby avoiding unintended side effects in other cellular compartments.
我们展示了人类细胞摄取碳纳米点(CND)后溶酶体的功能研究。即使在高CND浓度下,通过组织蛋白酶B和L以及自噬标志物SQSTM1/p62和LC3B-II表征的溶酶体功能仍得以维持。此外,支化聚乙烯亚胺(bPEI)分子已与CND偶联,作为一种功能化模型或药物示例。我们观察到,与单独的bPEI或CND相比,bPEI-CND缀合物在溶酶体中的积累程度更高。在此,观察到溶酶体大小和功能的变化,这完全可以由bPEI来解释。得出的结论是,CND是将功能分子高效且惰性地转运至溶酶体靶点的载体,其附加价值在于抑制了溶酶体逃逸,从而避免了在其他细胞区室中产生意外的副作用。