Walther Cornelia, Meyer Karolin, Rennert Robert, Neundorf Ines
Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Brüderstr. 34, 04103 Leipzig.
Bioconjug Chem. 2008 Dec;19(12):2346-56. doi: 10.1021/bc800172q.
We developed multifunctional fluorescent nanoparticles suitable for the nonviral delivery of negatively charged molecules like RNA. Therefore, we incorporated the recently developed branched hCT-derived carrier peptide hCT(18-32)-k7 on the surface of luminescent quantum dots (QDs). Besides detailed characterization of our QD-peptide conjugates concerning stability, toxicity, and uptake mechanism. we used them for efficient RNA delivery into different cell lines. The results of our studies indicate the involvement of more than one endocytotic uptake pathway in the internalization process. Furthermore, we could show that the QD-peptide bioconjugates exhibit no effect on cell viability and possess high stability inside living cells. The efficacy of our newly designed constructs for oligonucleotide drug delivery is highlighted by the successful intracellular transport of Cy-3 labeled RNA. Moreover, by using the chemotherapeutic chloroquine the efficient release of the assemblies out of endosomes was demonstrated. These results prove that our multifunctional platforms are versatile tools for diagnostic and therapeutic imaging purposes applicable for biologically active siRNA or aptamer sequences.
我们开发了适用于非病毒递送带负电荷分子（如RNA）的多功能荧光纳米颗粒。因此，我们将最近开发的分支hCT衍生载体肽hCT(18 - 32)-k7掺入发光量子点（QD）表面。除了对我们的QD - 肽缀合物在稳定性、毒性和摄取机制方面进行详细表征外，我们还将它们用于将RNA高效递送至不同细胞系。我们的研究结果表明，内化过程涉及不止一种内吞摄取途径。此外，我们可以证明QD - 肽生物缀合物对细胞活力没有影响，并且在活细胞内具有高稳定性。Cy - 3标记的RNA成功的细胞内转运突出了我们新设计的构建体用于寡核苷酸药物递送的功效。此外，通过使用化疗药物氯喹，证明了组装体从内体的有效释放。这些结果证明，我们的多功能平台是适用于生物活性siRNA或适体序列的诊断和治疗成像目的的通用工具。
