Exploiting the Nanoparticle Plasmon Effect: Observing Drug Delivery Dynamics in Single Cells via Raman/Fluorescence Imaging Spectroscopy

Abstract

Drug delivery systems (DDSs) offer efficient and localized drug transportation as well as reduce associated side effects. In order to better understand DDSs, precise observation of drug release and delivery is required. Here, we present a strategy, plasmonic-tunable Raman/fluorescence imaging spectroscopy, to track the release and delivery of an anticancer drug (doxorubicin) from gold nanoparticle carriers in real time at a single living cell level. A pH-responsive drug release profile was attained through the conjugation of doxorubicin (DOX) to the nanoparticle surface via a pH-sensitive hydrazone linkage. When DOX is bound to the surface of the gold nanoparticle, its surface-enhanced Raman spectrum can be seen, but its fluorescence is quenched. When released, due to the lysosomes' acidic pH, its Raman enhancement is greatly reduced, changing the acquired Raman spectrum and in turn allowing for the visualization of its fluorescence signal. The plasmonic-tunable Raman/fluorescence properties enabled the tracking of the DOX release and delivery process from the gold nanoparticle surface to the lysosomes of single living cells under the acidic pH change of their microenvironments. This technique offers great potential to follow the molecular mechanisms of drug delivery and release in living cells, as well as the cellular response to drug action.

Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

“…After washing with PBS, specimens were mounted in transparent mounting medium (VECTASHIELD; Vector Laboratories Inc., Burlingame, CA, USA) prior to LSCM analysis by a ZEISS LSM 510 Meta confocal microscope equipped with a Zeiss Zen software (Carl Zeiss, Oberkochen, Germany). DOX delivery and release was evaluated by monitoring the red fluorescence within the cells' body, 45 while PEG-AuNPs were imaged in reflectance mode at λ exc =561 nm as previously described. 16 In reflectance mode, the scattered light is collected under single laser wavelength excitation using a confocal microscope.…”

Directional emission from a single plasmonic scatterer

“…Nanoantennas composed of metallic nanoparticles that support localized surface plasmon resonances (LSPRs) in the ultraviolet-visible-infrared part of the electromagnetic spectrum have been used to control spontaneous emission [2][3][4][5][6] and surface enhanced Raman scattering 7,8 , and find applications in targeted medicine 9,10 , solar steam generation 11,12 or photovoltaics 13 . In many of these applications the directionality of the plasmon scattering plays a pivotal role.…”

Polyethylene glycol gold-nanoparticles: Facile nanostructuration of doxorubicin and its complex with DNA molecules for SERS detection

“…In the case of guanine, the band at 1467 cm -1 is caused by the C8H-N9C8 and C8N7 guanine group vibrations 38,39 . .…”