Direct Functionalization of Polysaccharide-Based Xylan Phenyl Carbonate Nanoparticles with Tumor Cell Specific Antibodies.

An efficient and easy-to-use approach is presented for obtaining biocompatible polysaccharide-based nanoparticles (NP) that can act as tumor-specific drug delivery agents. Two antibodies are directly immobilized onto reactive xylan phenyl carbonate (XPC) NP; namely Cetuximab (CTX) that binds to human epidermal growth factor receptor (EGFR) and Atezolizumab (ATZ) that binds to programmed death-ligand 1 (PD-L1). High coupling efficiency (up to 100 %) are achieved without any pre-activation and no aggregation occurs during antibody immobilization. By quartz crystal microbalance experiments with dissipation monitoring (QCM-D), flow cytometry assays, and confocal laser scanning microscopy imaging it is demonstrated that the functionalized XPC-NP specifically bind to cells carrying the corresponding antigens. Moreover, the NP retain the antibody specific bioactivities (growth inhibition for CTX and induction of T-cell cytotoxicity for ATZ).

Electrospun PCL Scaffolds as Drug Carrier for Corneal Wound Dressing Using Layer-by-Layer Coating of Hyaluronic Acid and Heparin.

Due to its ability to reduce scarring and inflammation, human amniotic membrane is a widely used graft for wound dressings after corneal surgery. To overcome donor dependency and biological variances in the donor tissue, artificial nanofibrous grafts acting as drug carrier systems are promising substitutes. Electrospun nanofibrous scaffolds seem to be an appropriate approach as they offer the properties of permeable scaffolds with a high specific surface, the latter one depending on the fiber diameter. Electrospun scaffolds with fiber diameter of 35 nm, 113 nm, 167 nm and 549 nm were manufactured and coated by the layer-by-layer (LbL) technology with either hyaluronic acid or heparin for enhanced regeneration of corneal tissue after surgery. Studies on drug loading capacity and release kinetics defined a lower limit for nanofibrous scaffolds for effective drug loading. Additionally, scaffold characteristics and resulting mechanical properties from the application-oriented characterization of suture pullout from suture retention tests were examined. Finally, scaffolds consisting of nanofibers with a mean fiber diameter of 113 nm were identified as the best-performing scaffolds, concerning drug loading efficiency and resistance against suture pullout.

Fluorescence labeled microbubbles for multimodal imaging.

Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-µCT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging.