Dye labeling for optical imaging biases drug carriers' biodistribution and tumor uptake.

Biodistribution analyses of nanocarriers are often performed with optical imaging. Though dye tags can interact with transporters, e.g., organic anion transporting polypeptides (OATPs), their influence on biodistribution was hardly studied. Therefore, this study compared tumor cell uptake and biodistribution (in A431 tumor-bearing mice) of four near-infrared fluorescent dyes (AF750, IRDye750, Cy7, DY-750) and dye-labeled poly(N-(2-hydroxypropyl)methacrylamide)-based nanocarriers (dye-pHPMAs). Tumor cell uptake of hydrophobic dyes (Cy7, DY-750) was higher than that of hydrophilic dyes (AF750, IRDye750), and was actively mediated but not related to OATPs. Free dyes' elimination depended on their hydrophobicity, and tumor uptake correlated with blood circulation times. Dye-pHPMAs circulated longer and accumulated stronger in tumors than free dyes. Dye labeling significantly influenced nanocarriers' tumor accumulation and biodistribution. Therefore, low-interference dyes and further exploration of dye tags are required to achieve the most unbiased results possible. In our assessment, AF750 and IRDye750 best qualified for labeling hydrophilic nanocarriers.

Monitoring the Remodeling of Biohybrid Tissue-Engineered Vascular Grafts by Multimodal Molecular Imaging.

Tissue-engineered vascular grafts (TEVGs) with the ability to grow and remodel open new perspectives for cardiovascular surgery. Equipping TEVGs with synthetic polymers and biological components provides a good compromise between high structural stability and biological adaptability. However, imaging approaches to control grafts' structural integrity, physiological function, and remodeling during the entire transition between late in vitro maturation and early in vivo engraftment are mandatory for clinical implementation. Thus, a comprehensive molecular imaging concept using magnetic resonance imaging (MRI) and ultrasound (US) to monitor textile scaffold resorption, extracellular matrix (ECM) remodeling, and endothelial integrity in TEVGs is presented here. Superparamagnetic iron-oxide nanoparticles (SPION) incorporated in biodegradable poly(lactic-co-glycolic acid) (PLGA) fibers of the TEVGs allow to quantitatively monitor scaffold resorption via MRI both in vitro and in vivo. Additionally, ECM formation can be depicted by molecular MRI using elastin- and collagen-targeted probes. Finally, molecular US of αv ß3 integrins confirms the absence of endothelial dysfunction; the latter is provocable by TNF-α. In conclusion, the successful employment of noninvasive molecular imaging to longitudinally evaluate TEVGs remodeling is demonstrated. This approach may foster its translation from in vitro quality control assessment to in vivo applications to ensure proper prostheses engraftment.