This work presents a method of industrially viable processing of nanocellulose-reinforced polyamide 6 (PA 6). Cellulose nanocrystal (CNC)reinforced PA 6 is gaining attention as a promising material for use in the automotive industry due to its highly crystalline, low density, and environmentally friendly nature. However, the low-thermal degradation temperature of CNCs presents problems when melt processing at high temperatures, making it difficult to produce the nanocomposite on a large scale. This article presents a methodology of master batching (MB) using planetary ball milling to embed the CNCs in PA 6. The process of MB CNCs with PA 6 to thermally buffer them was compared to direct milling and hand mixing, prior to melt processing with compression molding. The milled composites had final CNC compositions of either 5 or 10 wt%. Through thermal analysis, it was seen that although both milling methods thermally buffered the CNCs, the presence of the low-molecular weight PA 6 in the MB samples resulted in higher thermal stability. In addition to this, the mechanical analysis showed that the MB samples with 5 wt% CNCs had optimum Young's moduli, ultimate tensile strength, and elongation % at break. Overall, the use of milling for MB to coat the CNCs in polymer is a promising alternative to traditional processes and has potential as a method of industrially manufacturing cellulose reinforced polymer composites.
Antibody pretargeting is a promising strategy for improving molecular imaging, wherein the separation in time of antibody targeting and radiolabeling can lead to rapid attainment of high contrast, potentially increased sensitivity, and reduced patient radiation exposure. The inverse electron demand Diels-Alder ‘click’ reaction between trans-cyclooctene (TCO) conjugated antibodies and radiolabeled tetrazines presents an ideal platform for pretargeted imaging due to rapid reaction kinetics, bioorthogonality, and potential for optimization of both slow and fast clearing components. Herein, we evaluated a series of anti-human epidermal growth factor receptor 2 (HER2) pretargeting antibodies containing distinct molar ratios of site-specifically incorporated TCO. The effect of stoichiometry on tissue distribution was assessed for pretargeting TCO-modified antibodies (monitored by 125I) and subsequent accumulation of an 111In-labeled tetrazine in a therapeutically relevant HER2+tumor-bearing mouse model. Single photon emission computed tomography (SPECT) imaging was also employed to assess tumor imaging at various TCO-to-monoclonal antibody (mAb) ratios. Increasing TCO-to-mAb molar ratios correlated with increased in vivo click reaction efficiency evident by increased tumor distribution and systemic exposure of 111In-labeled tetrazines. The pharmacokinetics of TCO-modified antibodies did not vary with stoichiometry. Pretargeted SPECT imaging of HER2-expressing tumors using 111In-labeled tetrazine demonstrated robust click reaction with circulating antibody at ~2 hours and good tumor delineation for both the 2 and 6 TCO-to-mAb ratio variants at 24 hours, consistent with a limited cell-surface pool of pretargeted antibody and benefit from further distribution and internalization. To our knowledge, this represents the first reported systematic analysis of how pretargeted imaging is affected solely by variation in click reaction stoichiometry through site-specific conjugation chemistry.
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