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. 2015 Apr;36(7):694-9.
doi: 10.1002/marc.201500022. Epub 2015 Mar 9.

Luminescent difluoroboron β-diketonate PEG-PLA oxygen nanosensors for tumor imaging

Jelena Samonina-Kosicka  1 , Douglas H Weitzel, Christina L Hofmann, Hansford Hendargo, Gabi Hanna, Mark W Dewhirst, Gregory M Palmer, Cassandra L Fraser
Affiliations

Luminescent difluoroboron β-diketonate PEG-PLA oxygen nanosensors for tumor imaging

Jelena Samonina-Kosicka et al. Macromol Rapid Commun. 2015 Apr.

Abstract

Surface modification of nanoparticles and biosensors is a dynamic, expanding area of research for targeted delivery in vivo. For more efficient delivery, surfaces are PEGylated to impart stealth properties, long circulation, and enable enhanced permeability and retention (EPR) in tumor tissues. Previously, BF2 dbm(I)PLA was proven to be a good oxygen nanosensor material for tumor hypoxia imaging in vivo, though particles were applied directly to the tumor and surrounding region. Further surface modification is needed for this dual-emissive oxygen sensitive material for effective intravenous (IV) administration and passive and active delivery to tumors. In this paper, an efficient synthesis of a new dual-emissive material BF2 dbm(I)PLA-mPEG is presented and in vitro stability studies are conducted. It is found that fabricated nanoparticles are stable for 24 weeks as a suspension, while after 25 weeks the nanoparticles swell and both dye and polymer degradation escalates. Preliminary studies show BF2 dbm(I)PLA-mPEG nanoparticle accumulation in a window chamber mammary tumor 24 h after IV injection into mice (C57Bl/6 strain) enabling tumor oxygen imaging.

Keywords: boron beta diketonate; luminescence; nanoparticles; oxygen sensing; poly(ethylene glycol)-poly(lactic acid)s.

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Figures

Figure 1
Figure 1
GPC trace of reaction progress for the coupling of BF2dbm(I)PLA with mPEG-COOH.
Figure 2
Figure 2
BF2dbm(I)PLA-mPEG nanoparticle degradation. (A) Nanoparticle hydrodynamic radius (Rh) and polydispersity (PD) versus time measured by DLS. (B) Polymer molecular weight (Mn) and polydispersity index (PDI ) versus time measured by GPC. (C) Dye degradation measured by UV/Vis and fluorescence spectroscopy (λex = 369 nm).
Figure 3
Figure 3
Oxygen calibration. (A) Total emission spectra for different oxygen percentages (0–21% O2). (B) Fluorescence to phosphorescence intensity maxima ratio (F/P) versus oxygen concentration plot. (C) Mammary tumor window. Pictures shows images in bright field and optical imaging at 470 nm with BF2dbm(I)PLA-mPEG prior to injection and 24 hours after injection. (D) Combined F/P image from panel C with ratios indicating in vivo oxygen levels. (red: higher O2; blue: lower O2)
Scheme 1
Scheme 1
BF2dbm(I)PLA-mPEG Synthesis.
See this image and copyright information in PMC

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