期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 6, 页码 1862-1867出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1112132109
关键词
imaging; lanthanides; multimodal probes; pH low insertion peptide
资金
- Physical Sciences of Imaging in the Biomedical Sciences (PSIBS) Engineering and Physical Sciences Research Council Doctoral Training Centre
- British Heart Foundation
- Engineering and Physical Sciences Research Council
- European Regional Development Fund (ERDF)
- Advantage West Midlands (AWM)
- Birmingham Science City: Innovative Uses for Advanced Materials in the Modern World (West Midlands Centre for Advanced Materials Project 2)
- EPSRC [EP/G032262/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/G032262/1] Funding Source: researchfish
- Medical Research Council [G9818340B] Funding Source: researchfish
Water soluble, luminescent gold nanoparticles are delivered into human platelets via a rapid, pH-controlled mechanism using a pH low insertion peptide, pHLIP. The approach introduces cocoating of gold nanoparticles with a europium luminescent complex, EuL and the pHLIP peptide to give pHLIP.EuL.Au. The 13-nm diameter gold nanoparticles act as a scaffold for the attachment of both the luminescent probe and the peptide to target delivery. Their size allows delivery of approximately 640 lanthanide probes per nanoparticle to be internalized in human platelets, which are not susceptible to transfection or microinjection. The internalization of pHLIP.EuL.Au in platelets, which takes just minutes, was studied with a variety of imaging modalities including luminescence, confocal reflection, and transmission electron microscopy. The results show that pHLIP.EuL.Au only enters the platelets in low pH conditions, pH 6.5, mediated by the pHLIP translocation across the membrane, and not at pH 7.4. Luminescence microscopy images of the treated platelets show clearly the red luminescence signal from the europium probe and confocal reflection microscopy confirms the presence of the gold particles. Furthermore, transmission electron microscopy gives a detailed insight of the internalization and spatial localization of the gold nanoparticles in the platelets. Thus, we demonstrate the potential of the design to translocate multimodal nanoparticle probes into cells in a pH dependent manner.
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