No abstract

Purpose: Plastics are used commonly in the world because of its convenience and costeffectiveness. Microplastics, an environmental threat and human health risk, are widely detected in food, and consequently ingested. However degraded plastics are found everywhere, which cause environmental threat and human health risk. Therefore, real-time monitoring of orally administered microplastics is tremendously important to trace them in the body.Methods: In this study, to visualize their absorption path, we labeled polystyrene with [ 64 Cu]Cu-DOTA. We prepared radiolabeled polystyrene with 64 Cu after, [ 64 Cu]Cu-DOTApolystyrene was then orally administered to mice and evaluate its transit and absorption in mice using PET imaging. The absorption path and distribution of [ 64 Cu]Cu-DOTA-polystyrene were determined using positron emission tomography (PET) over 48 h. Ex vivo tissue-radio thin-layer chromatography (Ex vivo-radioTLC) was used to demonstrate the existence of [ 64 Cu]Cu-DOTApolystyrene in tissue. Results: PET images demonstrated that [ 64 Cu]Cu-DOTA-polystyrene began to transit to the intestine within 1 h. [ 64 Cu]Cu-DOTA-polystyrene accumulation in the liver was also observed. Biodistribution of [ 64 Cu]Cu-DOTA-polystyrene confirmed the observed distribution of [ 64 Cu]Cu-DOTA-polystyrene from PET images. Ex vivo-radioTLC was used to demonstrate that the detected gamma rays originated from [ 64 Cu]Cu-DOTA-polystyrene. Conclusion:This study provided evidence of microplastic accumulation and existence in tissue by using PET imaging, and cross confirmed by ex vivo-radioTLC. The information provided may be used as the basis for future studies on the toxicity of microplastics.

Background: Microplastics (MPs) are a new global environmental threat. Previously, we showed the biodistribution of MPs using [ 64 Cu] polystyrene (PS) and PET in mice. Here, we aimed to identify whether PS exposure has malignant effects on the stomach and induces resistance to therapy. Methods: BALB/c nude mice were fed 1.72 × 10 4 particles/mL of MP. We investigated PS accumulation in the stomach using radioisotope-labeled and fluorescent-conjugated PS. Further, we evaluated whether PS exposure induced cancer stemness and multidrug resistance, and whether it affected tumor development, tumor growth, and survival rate in vivo using a 4-week PS-exposed NCI-N87 mouse model. Using RNA-Seq analysis, we analyzed whether PS exposure induced gene expression changes in gastric tissues of mice. Results: PET imaging results showed that a single dose of [ 64 Cu]-PS remained for 24 h in the mice stomach. The 4-week daily repetitive dose of fluorescent conjugated PS was deposited in the gastric tissues of mice. When PS was exposed, a 2.9-fold increase in migration rate was observed for NCI-N87 cells. Immunocytochemistry results showed decreased E-cadherin and increased N-cadherin expression, and flow cytometry, qPCR, and western blot analysis indicated a 1.9-fold increase in N-cadherin expression after PS exposure . Further, PS-induced multidrug resistance to bortezomib, paclitaxel, gefitinib, lapatinib, and trastuzumab was observed in the NCI-N87 mouse model due to upregulated CD44 expression. RNA-seq results identified increased asialoglycoprotein receptor 2 ( ASGR2 ) expression after PS exposure, and ASGR2 knockdown decreased cell proliferation, migration, invasion, and drug resistance. Conclusion: We demonstrated that ASGR2 enhanced cancer hallmarks on PS exposure and induced resistance to chemo- and monoclonal antibody-therapy. Our preclinical findings may provide an incentive for further epidemiological studies on the role of MP exposure and its association with gastric cancer.