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Photoacoustic Imaging Quantifies Drug Release from Nanocarriers via Redox Chemistry of Dye-Labeled Cargo.

Angewandte Chemie (International ed. in English) (2019-12-17)
Ananthakrishnan Soundaram Jeevarathinam, Jeanne E Lemaster, Fang Chen, Eric Zhao, Jesse V Jokerst
ABSTRACT

We report a new approach to monitor drug release from nanocarriers via a paclitaxel-methylene blue conjugate (PTX-MB) with redox activity. This construct is in a photoacoustically silent reduced state inside poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PTX-MB@PLGA NPs). During release, PTX-MB is spontaneously oxidized to produce a concentration-dependent photoacoustic signal. An in vitro drug-release study showed an initial burst release (25 %) between 0-24 h and a sustained release between 24-120 h with a cumulative release of 40.6 % and a 670-fold increase in photoacoustic signal. An in vivo murine drug release showed a photoacoustic signal enhancement of up to 649 % after 10 hours. PTX-MB@PLGA NPs showed an IC50 of 78 μg mL-1 and 44.7±4.8 % decrease of tumor burden in an orthotopic model of colon cancer via luciferase-positive CT26 cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DL-Dithiothreitol, ≥99.0% (RT)
Sigma-Aldrich
Poly(vinyl alcohol), average Mw 31,000-50,000, 87-89% hydrolyzed
Sigma-Aldrich
Succinic anhydride, for synthesis
SAFC
RPMI-1640 Medium, with 2.05 mM L-glutamine, with 25mM HEPES, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Resomer® RG 504, Poly(D,L-lactide-co-glycolide), lactide:glycolide 50:50, ester terminated, Mw 38,000-54,000
Supelco
Ascorbic Acid, Meets ACS Specifications GR ACS