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Introduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly., Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated., Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies., Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Du et al.)

Curcumin (CUR) is a promising natural compound in ulcerative colitis (UC) treatment, but limited by its low oral bioavailability and poor targeting ability. Therefore, given the targeting action of lactoferrin (LF) by binding to the LF receptors of intestinal epithelial cells (IECs) and of folic acid (FA) by binding to the FA receptors of macrophages, we developed an oral dual-targeting nanosystem. Laminarin (LA)-coated, FA-modified LF nanoparticles (NPs) were used to encapsulate CUR (LA/FA/CUR-NPs) with a food-grade, enzyme-sensitive, and dual-targeting capacity. For the generated NPs, LF improved the loading efficiency of CUR (95.08 %). The LA layer could improve the upper gastrointestinal tract stability of the NPs while improve drug release around colon lesion through β-glucanase digestion. Based on the cellular uptake evaluation, FA/CUR-NPs were capable of specifically targeting colonic epithelial cells and macrophages through LF and FA ligands, respectively, to enhance the uptake efficiency. Moreover, based on the advantage of the dual-targeting strategy, oral administration of FA/CUR-NPs obviously reduced colitis symptoms by alleviating inflammation, accelerating colonic mucosal barrier repair and restoring the balance of the intestinal microbiota. This dual-targeted nanodesign corresponded to the multi-bioresponsibilities of CUR, thus offering a promising approach in UC treatment., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Herein, a β-1,3-d-glucan based microcarrier, yeast cell wall microparticles (YPs), was used to develop a food-source-based nano-in-micro oral delivery system for ulcerative colitis (UC) treatment. Briefly, lactoferrin (Lf), which targets intestinal epithelial cells, was used to encapsulate emodin (EMO) to form nanoparticles (EMO-NPs), and then loaded into YPs with the natural macrophages targeting ability, forming a final formula with two outer-inner targeting layers (EMO-NYPs). These dual-targeting strategy could enhance the dual-effects of EMO in anti-inflammatory and mucosal repair effects respectively. As expected, cell uptake assessment confirmed that EMO-NPs and EMO-NYPs could target on the Lf and dection-1 receptors on the membranes of Caco-2 cells and macrophages, respectively. Importantly, EMO-NYPs showed the best anti-UC effects compared to EMO-NPs and free EMO, by inhibiting NF-κB pathway to anti-inflammation and promoting intestinal mucosa repair via MLCK/pMLC2 pathway. The results show that EMO-NYPs are a promising food-based oral delivery system in anti-UC., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Existing nanoparticle-mediated drug delivery systems for glioma systemic chemotherapy remain a great challenge due to poor delivery efficiency resulting from the blood brain barrier/blood-(brain tumor) barrier (BBB/BBTB) and insufficient tumor penetration. Here, we demonstrate a distinct design by patching doxorubicin-loaded heparin-based nanoparticles (DNs) onto the surface of natural grapefruit extracellular vesicles (EVs), to fabricate biomimetic EV-DNs, achieving efficient drug delivery and thus significantly enhancing antiglioma efficacy. The patching strategy allows the unprecedented 4-fold drug loading capacity compared to traditional encapsulation for EVs. The biomimetic EV-DNs are enabled to bypass BBB/BBTB and penetrate into glioma tissues by receptor-mediated transcytosis and membrane fusion, greatly promoting cellular internalization and antiproliferation ability as well as extending circulation time. We demonstrate that a high-abundance accumulation of EV-DNs can be detected at glioma tissues, enabling the maximal brain tumor uptake of EV-DNs and great antiglioma efficacy in vivo.

Gliomas-devastating intracranial tumors with a dismal outcome-are in dire need of innovative treatment. Although nanodrugs have been utilized as a target therapy for certain types of solid tumors, their therapeutic effects in gliomas are limited due to the complications of the systemic circulation, blood-brain barrier (BBB), and specific glioma environment. Thus, we aimed to establish a nanoliposome adaptable to different environments by codelivery of shCD163 and doxorubicin (DOX) to treat gliomas. In this study, we first synthesized pH-sensitive DSPE-cRGD-Hz-PEG 2000 to form an environmentally self-adaptative nanoliposome (cRGD-DDD Lip) via a thin film method. We used in vitro BBB models, in vitro cell uptake experiments, and in vivo biodistribution assays to confirm the long circulation time and low cell uptake of the cRGD-DDD Lip as a result of the poly(ethylene glycol) (PEG) shell of cRGD-DDD Lip in the neutral pH systemic circulation. Moreover, the cRGD-DDD Lip bypassed the BBB and attached to the intracranial glioma following the removal of the PEG shell and the exposure of cRGD to the weakly acidic tumor microenvironment. We further assembled the shCD163/DOX@cRGD-DDD Lip through cRGD-DDD Lip loading of shCD163 and DOX. In vitro , cell proliferation and self-renewal of glioma cells were inhibited by the shCD163/DOX@cRGD-DDD Lip due to the toxicity of DOX and the suppression of shCD163 via the CD163 pathway. In vivo , the shCD163/DOX@cRGD-DDD Lip disturbed the progression of in situ gliomas by inhibiting the growth and stemness of glioma cells and prevented the recurrence of gliomas after resection. In conclusion, the cRGD-DDD Lip may be a promising nanodrug-loading platform to cope with different environments and the shCD163/DOX@cRGD-DDD Lip may potentially be a novel nanodrug for glioma therapy.

Cellular internalization, delivery efficiency, and therapeutic efficacy of nanoparticles vary according to the microenvironmental complexity for tumor types. Adjusting their physicochemical properties, such as surface properties and size, has significant potential for dealing with such complexities. Herein, we prepare four types of pH-sensitive doxorubicin nanoparticles (DOX-D1, DOX-D2, DOX-W1, and DOX-W2 Nano) using simply changing reaction medium or reactant ratio. DOX-D1 and DOX-D2 Nano exhibit similar surface characteristics (surface coating and targeting ligand content) and different size, while both DOX-W Nano examples present similar surface characteristics and size. And they can re-self-assemble into smaller particles in blood-mimic conditions and the order of size is as follows: DOX-D1> DOX-D2 ≈ DOX-W Nano, and DOX-W Nano has a higher targeting ligand content than DOX-D Nano. Thus, the bioactivities in vitro and tumor microenvironment responses of DOX-D1, DOX-D2, and DOX-W1 are further investigated due to their different physicochemical properties. DOX-W1 Nano exhibits a higher cellular uptake, a stronger antiproliferation than DOX-D1 and DOX-D2 Nano attributed to its smaller size, and a higher targeting moiety content. Despite the similar sizes of DOX-W1 and DOX-D2, DOX-D2 Nano shows a greater in vitro blood-brain barrier (BBB) permeability related to its surface coating. Interestingly, DOX-D1 with suitable size and surface property can efficiently bypass the BBB and deliver to an intracranial glioma; in comparison DOX-W1 Nano has excellent targeting efficiency in subcutaneous tumors (glioma and breast cancer). Accordingly, DOX-D1 Nano is preferential for the treatment of intracranial glioma while DOX-W1 Nano exhibits potent killing ability for subcutaneous tumors. Our work suggests tailoring multiple physicochemical properties of nanoparticles can play a significant role in addressing tumor microenvironment complexity.