Uptake of Nanoplastic particles by zebrafish embryos triggers the macrophage response at early developmental stage.

Plastic pollution continues to erupt as a global ecological concern. As plastic debris is degraded into nanoscale and microscale particles via biodegradation, UV-irradiation, and mechanical processes, nanoplastic pollution arises as a threat to virtually every biological and ecological system on the planet. In this study, zebrafish (Danio rerio) embryos were exposed to fluorescently labeled plastic particles at nanoscales (30 nm and 100 nm). The uptake of both the nanoplastic particles (NPs) was found to exponentially increase with incubation time. Penetration of NPs through the natural barrier of the zebrafish embryos, the chorion, was observed prior to the hatching of the embryo. As a result, the NPs were found to accumulate on the body surface as well as inside the body of the zebrafish. The invasion of NPs into zebrafish embryos induced the upregulation of several stress and immune response genes including interleukins (il6 and il1b), cytochrome P450 (cyp1a and cyp51), and reactive oxygen species (ROS) removal protein-encoding genes (sod and cat). This suggested the initiation of ROS generation and removal as well as the activation of the immune response of zebrafish embryos. Colocalization of macrophages and NPs in zebrafish embryos indicated the involvement of macrophage response to the NP invasion at the early developmental stage of zebrafish.

Targeting Tumor-Associated Macrophages by MMP2-Sensitive Apoptotic Body-Mimicking Nanoparticles.

Tumor-associated macrophages (TAMs), a major player in the tumor microenvironment, were recently recognized as a potential therapeutic target. To date, very few anticancer drugs or drug-delivery systems were designed to target the TAMs. Inspired by the "eat me" signal, phosphatidylserine (PS), mediated phagocytic clearance of apoptotic bodies, in this study, the matrix metalloproteinase 2 (MMP2)-sensitive PS-modified nanoparticles were developed. In the design, the PS is externalized to the nanoparticles' surface only when the nanoparticles reach the MMP2-overexpressing tumor site, allowing for the TAM-specific phagocytosis. The nanoparticles' excellent macrophage/TAM selectivity was observed in various biological models, including various cell lines, coculture cells, coculture cell spheroids, zebrafish, and tumor-bearing mice. The nanoparticles' TAM specificity remarkably enhanced the TAM depletion capability of the loaded model drug, dasatinib, resulting in the improved anticancer activity. The MMP2-sensitive apoptotic body-mimicking nanoparticles might be a promising delivery tool for TAM-centered cancer diagnoses and treatments.

Relationship between Rainfall, Fecal Pollution, Antimicrobial Resistance, and Microbial Diversity in an Urbanized Subtropical Bay.

Urbanized bays are vulnerable to fecal bacterial pollution, and the extent of this pollution, in marine recreational waters, is commonly assessed by quantifying enterococcus concentrations. Recent reports have questioned the utility of enterococci as an indicator of fecal bacterial pollution in subtropical bays impaired by non-point source pollution, and enterococcus data alone cannot identify fecal bacterial sources (i.e., hosts). The purpose of this study was to assess relationships between rainfall, fecal bacterial pollution, antimicrobial resistance, and microbial diversity in an urbanized subtropical bay. Thus, a comprehensive bacterial source tracking (BST) study was conducted using a combination of traditional and modern BST methods. Findings show that rainfall was directly correlated with elevated enterococcus concentrations, including the increased prevalence of Enterococcus faecium, although it was not correlated with an increase in the prevalence of antimicrobial-resistant strains. Rainfall was also correlated with decreased microbial diversity. In contrast, neither rainfall nor enterococcus concentrations were directly correlated with the concentrations of three omnipresent host-associated fecal markers (i.e., human, canine, and gull). Notably, the human fecal marker (HF183) was inversely correlated with enterococcus concentrations, signifying that traditional enterococcus data alone are not an accurate proxy for human fecal waste in urbanized subtropical bays.IMPORTANCE The presence of human enteric pathogens, stemming from fecal pollution, is a serious environmental and public health concern in recreational waters. Accurate assessments of fecal pollution are therefore needed to properly assess exposure risks and guide water quality policies and practices. In this study, the absence of a direct correlation between enterococci and source-specific human and animal markers disputes the utility of enterococci as an indicator of fecal pollution in urbanized subtropical bays. Moreover, the inverse correlation between enterococci and the human-specific marker HF183 indicates that recreational beach advisories, triggered by elevated enterococcus concentrations, are a misleading practice. This study clearly demonstrates that a multiparameter approach that includes the quantitation of host-specific markers, as well as analyses of microbial diversity, is a more effective means of assessing water quality in urbanized subtropical bays.