Quantum Dot-Carrier Peptide Conjugates Suitable for Imaging and Delivery Applications

被引:86
作者
Walther, Cornelia [1 ]
Meyer, Karolin [1 ]
Rennert, Robert [1 ]
Neundorf, Ines [1 ]
机构
[1] Univ Leipzig, Fac Biosci Pharm & Psychol, Inst Biochem, D-04103 Leipzig, Germany
关键词
D O I
10.1021/bc800172q
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2346 / 2356
页数:11
相关论文
共 45 条
[1]   Nanocrystal targeting in vivo [J].
Åkerman, ME ;
Chan, WCW ;
Laakkonen, P ;
Bhatia, SN ;
Ruoslahti, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (20) :12617-12621
[2]   Evaluation of cell-penetrating peptides (CPPs) as vehicles for intracellular delivery of antisense peptide nucleic acid (PNA) [J].
Bendifallah, Nadia ;
Rasmussen, Frank Winther ;
Zachar, Vladimir ;
Ebbesen, Peter ;
Nielsen, Peter E. ;
Koppelhus, Uffe .
BIOCONJUGATE CHEMISTRY, 2006, 17 (03) :750-758
[3]   Structure - Function correlation of chloroquine and analogues as transgene expression enhancers in nonviral gene delivery [J].
Cheng, Jianjun ;
Zeidan, Ryan ;
Mishra, Swaroop ;
Liu, Aijie ;
Pun, Suzie H. ;
Kulkarni, Rajan P. ;
Jensen, Gregory S. ;
Bellocq, Nathalie C. ;
Davis, Mark E. .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (22) :6522-6531
[4]   Self-assembled quantum dot-peptide bioconjugates for selective intracellular delivery [J].
Delehanty, James B. ;
Medintz, Igor L. ;
Pons, Thomas ;
Brunel, Florence M. ;
Dawson, Philip E. ;
Mattoussi, Hedi .
BIOCONJUGATE CHEMISTRY, 2006, 17 (04) :920-927
[5]   Targeted quantum dot conjugates for siRNA delivery [J].
Derfus, Austin M. ;
Chen, Alice A. ;
Min, Dal-Hee ;
Ruoslahti, Erkki ;
Bhatia, Sangeeta N. .
BIOCONJUGATE CHEMISTRY, 2007, 18 (05) :1391-1396
[6]   Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings [J].
Duan, Hongwei ;
Nie, Shuming .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (11) :3333-3338
[7]   A comprehensive model for the cellular uptake of cationic cell-penetrating peptides [J].
Duchardt, Falk ;
Fotin-Mleczek, Mariola ;
Schwarz, Heinz ;
Fischer, Rainer ;
Brock, Roland .
TRAFFIC, 2007, 8 (07) :848-866
[8]   Decoding the entry of two novel cell-penetrating peptides in HeLa cells: Lipid raft-mediated endocytosis and endosomal escape [J].
Foerg, C ;
Ziegler, U ;
Fernandez-Carneado, J ;
Giralt, E ;
Rennert, R ;
Beck-Sickinger, AG ;
Merkle, HP .
BIOCHEMISTRY, 2005, 44 (01) :72-81
[9]   Arginine-rich peptides and their internalization mechanisms [J].
Futaki, S. ;
Nakase, I. ;
Taclokoro, A. ;
Takeuchi, T. ;
Jones, A. T. .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2007, 35 :784-787
[10]   Targeting of nanoparticles to the clathrin-mediated endocytic pathway [J].
Harush-Frenkel, Oshrat ;
Debotton, Nir ;
Benita, Simon ;
Altschuler, Yoram .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 353 (01) :26-32