With worldwide environmental accumulation of plastics and their recognized degradation into smaller particles, attention to their impacts on ecological systems and humans has been increasing recently. However, environmental factors and their impacts are seldom considered during their eco-toxicity evaluation. In this study, D. magna neonates were used to assess and compare the acute toxicities of polystyrene microplastic particles (MPPs) and nanoplastic particles (NPPs) in the absence and presence of humic acids (HAs), an important environmental factor in aquatic systems. Four stress response and detoxification genes (CAT, GST, HSP70, and P-GP) were used to characterize the toxic response of the neonates to the exposure. Our results showed that NPPs were much more toxic than MPPs in that 10 mg L-1 NPPs induced over 70% of death in 96 h but MPPs (as high as 400 mg L-1) caused no mortality under all tested conditions. More importantly, we revealed a potent protective role of HA against NPP toxicity at environmentally relevant concentrations. The effect was concentration dependent, as 50 mg L-1 HA subdued the NPP (400 mg L-1) toxicity effect completely. NPPs elicited the up-regulation of all examined genes while HA diminished the change appreciably, further confirming its detoxifying role against NPP toxicity. Through fluorescence and dynamic light scattering measurements, we found that HA was adsorbed on NPPs and formed a corona, without causing agglomeration or precipitation, but changed NPP distribution in the D. magna neonates in a way similar to that of MPPs, leading to alleviated toxicity. Our results suggest that it is essential to consider environmental factors in evaluating and monitoring NPP toxicity as this presents a more relevant exposure state.

Abstract Background Stimulation of vascular endothelial growth factor (VEGF) has been observed following transarterial chemoembolization (TACE) in hepatocellular cancer (HCC) and may contribute to tumor regrowth. This pilot study examined whether intravenous (IV) bevacizumab, a monoclonal antibody against VEGF, could inhibit neovessel formation after TACE. Methods 30 subjects with HCC undergoing TACE at a single academic institution were randomized with a computer-generated allocation in a one to one ratio to either bevacizumab at a dose of 10 mg/kg IV every 14 days beginning 1 week prior to TACE (TACE-BEV arm) or observation (TACE-O arm). Angiography was performed with TACE at day 8, and again at weeks 10 and 14. Repeat TACE was performed at week 14 if indicated. TACE-BEV subjects were allowed to continue bevacizumab beyond week 16. TACE-O subjects were allowed to cross-over to bevacizumab at week 16 in the setting of progressive disease. The main outcome measure was a comparison of neovessel formation by serial angiography. Secondary outcome measures were progression free survival (PFS) at 16 weeks, overall survival (OS), bevacizumab safety, and an analysis of VEGF levels before and after TACE with and without bevacizumab. Results Among the 30 subjects enrolled, 9 of 15 randomized to the TACE-O arm and 14 of 15 randomized to the TACE-BEV arm completed all 3 angiograms. At week 14, 3 of 9 (33%) TACE-O subjects and 2 of 14 (14%) TACE-BEV subjects demonstrated neovascularity. The PFS at 16 weeks was 0.19 in the TACE-O arm and 0.79 in the TACE-BEV arm (p = 0.021). The median OS was 61 months in the TACE-O arm and 49 months in the TACE-BEV arm (p = 0.21). No life-threatening bevacizumab-related toxicities were observed. There were no substantial differences in bevacizumab pharmacokinetics compared to historical controls. Bevacizumab attenuated the increase in VEGF observed post-TACE. Conclusions IV bevacizumab was well tolerated in selected HCC subjects undergoing TACE, and appeared to diminish neovessel formation at week 14. Trial registration ClinicalTrials.gov NCT00049322.