{
    "abstract": "The mitochondrial potassium channel Kv1.3 is a critical therapeutic target, as its blockade induces cancer cell apoptosis, highlighting its therapeutic potential. PAP-1, a potent and selective membrane-permeant Kv1.3 inhibitor, faces solubility challenges affecting its bioavailability and antitumor efficacy. To circumvent these challenges, we developed a tumor-targeting drug delivery system by encapsulating PAP-1 within pH-responsive mPEG-PAE polymeric micelles. These self-assembled micelles exhibited high entrapment efficiency (91.35%) and drug loading level (8.30%). As pH decreased, the micelles exhibited a significant increase in particle size and zeta potential, accompanied by a surge in PAP-1 release. Molecular simulations revealed that PAE's tertiary amine protonation affected the self-assembly process, modifying hydrophobicity and resulting in larger, loosely packed particles. Furthermore, compared to free PAP-1 or PAP-1 combined with MDR inhibitors, PAP-1-loaded micelles significantly enhanced cytotoxicity and apoptosis induction in Jurkat and B16F10 cells, through mechanisms involving decreased mitochondrial membrane potential and elevated caspase-3 activity. ",
    "authors": [
        {
            "affiliation": "School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, P. R. China.",
            "firstname": "Fang",
            "initials": "F",
            "lastname": "Ye"
        },
        {
            "affiliation": "School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, P. R. China.\nDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, P. R. China.",
            "firstname": "Qi",
            "initials": "Q",
            "lastname": "Li"
        },
        {
            "affiliation": "School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, P. R. China.\nClinical Laboratory, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, P.R. China.",
            "firstname": "Longping",
            "initials": "L",
            "lastname": "Huang"
        },
        {
            "affiliation": "Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, P. R. China.",
            "firstname": "Naikai",
            "initials": "N",
            "lastname": "Liao"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1080/10717544.2025.2490269\n10.3892/or.9.5.961\n10.1517/13543776.2011.561784\n10.1085/jgp.20028607\n10.1016/j.toxicon.2014.05.002\n10.1016/j.bbrc.2010.06.011\n10.2174/156800909790192400\n10.3322/caac.21834\n10.1097/MPA.0b013e3181a56ebf\n10.3389/fonc.2022.865686\n10.1021/acsnano.3c03166\n10.1007/s00424-003-1077-0\n10.1016/j.jconrel.2021.02.031\n10.1002/med.21800\n10.1007/978-3-031-27156-4_3\n10.18632/oncotarget.27122\n10.1002/jcc.10128\n10.1172/JCI155938\n10.3390/cancers14081955\n10.1016/j.jconrel.2007.07.012\n10.1016/j.jaut.2014.07.003\n10.4161/cbt.4.12.2175\n10.1002/emmm.201200235\n10.1038/leu.2013.56\n10.1016/j.ccell.2017.03.003\n10.1002/adhm.202101407\n10.1021/acsnano.3c08485\n10.1016/j.biomaterials.2021.121076\n10.1002/jcc.21224\n10.3390/cancers15102716\n10.3181/0705-RM-148\n10.1016/j.redox.2020.101705\n10.1177/2472555219864894\n10.1080/03639045.2021.1934869\n10.1073/pnas.2013545118\n10.3233/JAD-141704\n10.1080/14728222.2017.1420170\n10.1021/acs.jpcb.5b00689\n10.1073/pnas.0804236105\n10.1002/jcc.20291\n10.1007/s42977-021-00071-7\n10.1159/000480643\n10.1016/j.bja.2020.06.027\n10.1002/jcc.20035\n10.34133/2022/9808429",
    "journal": "Drug delivery",
    "keywords": [
        "Mitochondrial potassium channel Kv1.3",
        "PAP-1",
        "anti-tumor",
        "pH-responsive",
        "polymeric micelles"
    ],
    "methods": null,
    "publication_date": "2025-04-10",
    "pubmed_id": "40207975\n12168055\n12926074\n21413912\n12084773\n24878374\n20570656\n20025600\n38572751\n19465885\n35402277\n37294705\n12838421\n33652113\n33932253\n37306903\n31448055\n12395429\n37166997\n35454865\n17894942\n25175978\n16258262\n22496117\n23426166\n28399409\n34601824\n38055669\n34461456\n19229944\n37345053\n17959847\n33007503\n31373829\n34033496\n33649184\n25362031\n29258373\n25853313\n15632141\n18818304\n16211538\n35998249\n34554500\n28869943\n32654743\n15116359\n36452433",
    "results": null,
    "title": "Reliable high-PAP-1-loaded polymeric micelles for cancer therapy: preparation, characterization, and evaluation of anti-tumor efficacy.",
    "xml": "<Element 'PubmedArticle' at 0x788502a1b4c0>"
}