Preparation and biological evaluation of multifunctional PLGA-nanoparticles designed for photoacoustic imaging.
Nanoparticulate contrast agents for molecular imaging have attracted widespread interest for diagnostic applications with high resolution in medicine. Here we introduce polymer-based multifunctional nanoparticles exhibiting a near-infrared absorption in the range of the Nd:YAG laser wavelength of 1064 nm as a novel resorbable photoacoustic (PA) contrast system and report about their biological evaluation. Submicron-sized spherical nanoparticles with a high encapsulation efficiency (>87%) were created by incorporation of near-infrared dyes (IR5/IR26) in poly[(rac-lactide)-co-glycolide] (PLGA) with 50 mol% glycolide content via a specific spray-drying process in good yield (>75%). Subsequent application of a centrifugation protocol produced two different size fractions with diameters in the ranges 445-540 nm and 253-305 nm; these were further used for investigation of PA properties and cytotoxic effects. The prepared PLGA nanoparticles exhibited PA properties using a Nd:YAG laser-based system. After exposure of particle concentrations up to 10 μg·ml(-1) for 2 days no effects on viability, mitochondrial activity and proliferation, and cell death of human hepatocarcinoma cells and monkey kidney cells were observed. The excellent PA properties in combination with the positive biological results qualify the dye-loaded PLGA particles as promising candidates for a resorbable PA contrast system.


BACKGROUND
Photoacoustics (PA), a new modality, in which laser light is shined into tissue and absorbed by inherent proteins or synthetic particles is reflected back and received as ultrasound. This technique was shown to be effective with an erodible polymer particle containing near infrared dyes. In vitro, the PA properties of the PLGA particles persisted for 2 days in cell culture.
Kohl
Yvonne
Y
Fraunhofer Institute for Biomedical Engineering, Division of Biohybrid Systems, St. Ingbert, Germany.
Kaiser
Christian
C
Bost
Wolfgang
W
Stracke
Frank
F
Fournelle
Marc
M
Wischke
Christian
C
Thielecke
Hagen
H
Lendlein
Andreas
A
Kratz
Karl
K
Lemor
Robert
R
D000162:Acoustics; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003287:Contrast Media / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000009:adverse effects / Q000737:chemistry*; D053844:Lasers, Solid-State; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000009:adverse effects / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019265:Spectroscopy, Near-Infrared; D014463:Ultrasonography; D014709:Vero Cells
D003287:Contrast Media; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid