pH-controlled delivery of luminescent europium coated nanoparticles into platelets.
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.
Physical Sciences of Imaging in the Biomedical Sciences (PSIBS) Doctoral Training Centre, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
Amy
A
Davies
David J
DJ
Lewis
Stephen P
SP
Watson
Steven G
SG
Thomas
Zoe
Z
Pikramenou
D001792:Blood Platelets / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005063:Europium / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D021621:Imaging, Three-Dimensional; D049449:Luminescence; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013056:Spectrophotometry, Ultraviolet
D008565:Membrane Proteins; C533201:pHLIP protein; D005063:Europium