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FOOD CHEMISTRY · 2023 · IF 8.8

Enhanced curcumin transportation across epithelial barrier by mucus-permeable soy protein nanoparticles-mediated dual transcytosis pathways

Dan Yuan,Qi Li,Qibo Zhang,Feibai Zhou,Qiangzhong Zhao,Mouming Zhao

Nanocarrier-delivered bioactive compounds are highly desirable for their improved stability and applicability, but their bioavailability is still limited due to the strong mucus and epithelial cell barriers. Herein, a series of self-assembled soy protein nanoparticles (SPNPs) with different mucus permeabilities were prepared and their delivery efficiency upon Curcumin (Cur) encapsulation was evaluated. Results demonstrated that the formed SPNPs-Cur exhibited high compatibility and cellular antioxidant accessibility. Besides, SPNPs enhanced the cellular uptake and transmembrane permeation of Cur, especially promoted the transportation of proto-Cur in addition to Cur metabolites. The SPNPs with the rapid mucus diffusion capacity presented more efficient transcytosis across the Caco-2 cell monolayer, which was mediated by a combination of paracellular and transcellular pathways. This work verified that mucus-permeable soy protein nanoparticles could be a promising delivery system for improving the bioavailability of bioactive compounds.

研究领域: 药剂学 · 生物医学工程 · 食品科学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Aggregation-induced emission-active iridium (III)-based mitochondria-targeting nanoparticle for two-photon imaging-guided photodynamic therapy

Xucan Yang,Lulu Cheng,Yile Zhao,Haoran Ma,Haitao Song,Xuanmin Yang,Kang-Nan Wang,Yanrong Zhang

The efficacy of imaging-guided photodynamic therapy (PDT) is compromised by the attenuation of fluorescence and decline in reactive oxygen species (ROS) generation efficiency in the physiological environment of conventional photosensitizers , limited near-infrared (NIR) absorption, and high systemic cytotoxicity. This paper presents the synthesis of two cyclometalated Ir (III) complexes (Ir-thpy and Ir-ppy) by using a triphenylamine derivative (DPTPA) as the primary ligand and their encapsulation into an amphiphilic phospholipid to form nanoparticles (NPs). These complexes exhibit aggregation-induced emission features and remarkably enhanced ROS generation compared to Chlorin e6 (Ce6). Moreover, Ir-thpy NPs possess the unique ability to selectively target mitochondria , leading to depolarization of the mitochondrial membrane potential and ultimately triggering apoptosis. Notably, Ir-thpy NPs exhibit exceptional photocytotoxicity even towards cisplatin-resistant A549/DDP tumor cells. In vivo two-photon imaging verified the robust tumor-targeting efficacy of Ir-thpy NPs. The in vivo results unequivocally demonstrate that Ir-thpy NPs exhibit excellent tumor ablation along with remarkable biocompatibility. This study presents a promising approach for the development of multifunctional Ir-NPs for two-photon imaging-guided PDT and provides novel insights for potential clinical applications in oncology.

研究领域: 材料科学 · 纳米技术 · 癌症研究 · 生物医学工程 · 药学
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AAPS PHARMSCITECH · 2023 ·Vol. 24 ·期 2 ·1-16 · IF 3.3

Transcellular Transport Behavior of the Intact Polymeric Mixed Micelles with Different Polymeric Ratios

Wu Wenting,Ding Quan,Zhou Zhiwei,Kuang Wenliang,Jiang Lipeng,Liu Peng,Ai Weiping,Zhu Weifeng

In order to better promote the application of the polymeric mixed micelles (PMMs) in oral delivery, in addition to focusing on the improvement of micellar structural stability, it is necessary to obtain the absorption characteristics of the intact micellar particles. In this work, the transport behavior across Caco-2 cells of FS/PMMs composed of Pluronic F127 and Solutol HS15 was tracked by encapsulating an environment-responsive probe into the particles. The specific property of the probe is the water-initiated aggregation-caused quenching (ACQ) ability, by which integral particles can be identified accurately. The influence of polymeric ratios (FS) on the transcellular behavior of FS/PMMs was explored and the single pass intestinal perfusion experiment was used to further illustrate it. Moreover, pharmacokinetics parameters were detected to analyze the relationship among FS ratios, transport behavior, and pharmacokinetic parameters. FS ratios were found to hardly affect the endocytosis pathways and intracellular itinerary of FS/PMMs, but do affect the proportion of each path. FS/PMMs with high HS15 content, namely System-I, were found to primarily undergo receptor-mediated endocytosis pathway and be less susceptible to lysosomal degradation, which would lead to more absorption and higher Cmax and AUC than drug suspension. In contrast, despite System-II with high F127 content cannot contribute to drug plasma concentration, it can prolong the in vivo retention time. These findings provided evidence for the role of polymeric ratios in modulating the transcellular absorption and pharmacokinetic parameters of the drug-loaded PMMs, and would be a step forward in helping PMMs’ design to enhance oral drug delivery. Graphical Abstract

研究领域: 药学 · 药物递送系统 · 药理学 · 生物药剂学
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Theranostics · 2024 · IF 12.4

Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies

Yixuan Huang,Jiacai Wu,Sanpeng Li,Zhen Liu,Zhenghua Li,Boping Zhou,Bin Li

Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms. Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated. Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature. Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.

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