{
    "abstract": "Acute rejection may manifest following heart transplantation, despite the implementation of relatively well-established immunosuppression protocols. The significance of the mTOR signaling pathway in rejection is widely acknowledged. BEZ235, a second-generation mTOR inhibitor with dual inhibitory effects on PI3K and mTOR, holds promise for clinical applications. This study developed a nanodelivery system, BEZ235@NP, to facilitate the intracellular delivery of BEZ235, which enhances efficacy and reduces adverse effects by improving the poor solubility of BEZ235. In the complete MHCII-mismatched model, BEZ235@NP significantly prolonged cardiac allografts survival compared to free BEZ235, which was attributed to more effective suppression of effector T cell activation and promotion of greater expansion of Tregs. These nanoparticles demonstrated excellent biosafety and exhibited no short-term biotoxicity upon investigation. To elucidate the mechanism, primary T cells were isolated from the spleen and it was observed that BEZ235@NP treatment resulted in the arrest of these cells in the G0/G1 phase. As indicated by Western blot analysis, BEZ235@NP substantially reduced mTOR phosphorylation. This, in turn, suppressed downstream pathways and ultimately exerted an anti-proliferative and anti-activating effect on cells. Furthermore, it was observed that inhibition of the mTOR pathway stimulated T-cell autophagy. In conclusion, the strategy of intracellular delivery of BEZ235 presents promising applications for the treatment of acute rejection.",
    "authors": [
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Kai",
            "initials": "K",
            "lastname": "Xing"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Yanjia",
            "initials": "Y",
            "lastname": "Che"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China. Electronic address: wangzhiwei@whu.edu.cn.",
            "firstname": "Zhiwei",
            "initials": "Z",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Shun",
            "initials": "S",
            "lastname": "Yuan"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Qi",
            "initials": "Q",
            "lastname": "Wu"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Feng",
            "initials": "F",
            "lastname": "Shi"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Yuanyang",
            "initials": "Y",
            "lastname": "Chen"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Xiaoyan",
            "initials": "X",
            "lastname": "Shen"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Xiaohan",
            "initials": "X",
            "lastname": "Zhong"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Xiaoping",
            "initials": "X",
            "lastname": "Xie"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Qingyi",
            "initials": "Q",
            "lastname": "Zhu"
        },
        {
            "affiliation": "Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Cardiovascular Surgery Laboratory, Renmin Hospital of Wuhan University, District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China; Central Laboratory, Renmin Hospital of Wuhan University. District No. 99, Zhang Road, Wuhan 430060, Hubei, PR China.",
            "firstname": "Xu",
            "initials": "X",
            "lastname": "Li"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2023 Elsevier B.V. All rights reserved.",
    "doi": "10.1016/j.intimp.2023.110922",
    "journal": "International immunopharmacology",
    "keywords": [
        "BEZ235",
        "Chitosan",
        "Heart transplantation",
        "Nanodelivery",
        "PI3K-mTOR dual inhibition",
        "T cells"
    ],
    "methods": null,
    "publication_date": "2023-09-13",
    "pubmed_id": "37699303",
    "results": null,
    "title": "Chitosan nanoparticles encapsulated with BEZ235 prevent acute rejection in mouse heart transplantation.",
    "xml": "<Element 'PubmedArticle' at 0x788505551ee0>"
}