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The emerging tumor-targeted delivery technology can facilitate the precise enrichment of drugs in the tumor site. Apolipoprotein E (ApoE(159\u2013167)\n                    <jats:sub>2<\/jats:sub>\n                    ) binds to low-density lipoprotein receptor-related protein 1 (LRP-1) on the blood\u2013brain barrier and helps it to specifically cross the BBB. Based on this, in this study, poly (ethylene glycol) (PEG) dimerized with ApoE(159\u2013167)\n                    <jats:sub>2<\/jats:sub>\n                    was used for the modification of PAH-AM, and amphiphilic PAH-AM-PEG-ApoE nanocarriers were successfully prepared. Among them, the PEG modification could effectively prolong the retention time of the nanoparticles\n                    <jats:italic>in vivo<\/jats:italic>\n                    and reduce the toxic side effects, while the ApoE(159\u2013167)\n                    <jats:sub>2<\/jats:sub>\n                    polypeptide could specifically penetrate the blood\u2013brain barrier for intracerebral targeted delivery by binding to LRP-1. The nanocarrier further binds to small interfering RNA (siRNA) targeting\n                    <jats:italic>PLK1<\/jats:italic>\n                    , a key cell cycle factor, by electrostatic interaction to construct the nano-delivery system PAPA@siPLK1.\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments showed that the nanoparticles significantly inhibited the proliferation of U87MG glioma cells, induced apoptosis, and specifically silenced the mRNA and protein expression of\n                    <jats:italic>PLK1<\/jats:italic>\n                    . The results of\n                    <jats:italic>in vivo<\/jats:italic>\n                    animal experiments showed that PAPA@siPLK1 could effectively inhibit tumor growth and had potential brain permeability; The PAPA@siPLK1 nanocarrier delivery system developed in this study achieves\n                    <jats:italic>PLK1<\/jats:italic>\n                    gene silencing through efficient siRNA delivery, providing an important basis for novel therapeutic strategies for glioma.\n                  <\/jats:p>","DOI":"10.1208\/s12249-025-03323-0","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T02:09:42Z","timestamp":1771466982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The PAH-AM-PEG-ApoE@siRNA Nanocarrier Delivery System for Polo-like Kinase 1 Inhibition Suppresses Glioma Progression"],"prefix":"10.1208","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5641-7115","authenticated-orcid":false,"given":"Feng","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3187-5010","authenticated-orcid":false,"given":"Shengnan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5352-8998","authenticated-orcid":false,"given":"Junli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3179-1249","authenticated-orcid":false,"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5604-3197","authenticated-orcid":false,"given":"Yaoyao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9402-338X","authenticated-orcid":false,"given":"Ling","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6057-6314","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7256-1138","authenticated-orcid":false,"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4667-8399","authenticated-orcid":false,"given":"Guangwei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-3136","authenticated-orcid":false,"given":"Lifang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"3323_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1586515","author":"Y Zeng","year":"2025","unstructured":"Zeng Y, Lu X, Wang Y, et al. 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Ethic Committee Name: Hubei Bennett Biotechnology Co., Ltd. Experimental Animal Ethics Committee. The ethical number for the experimental animals is: BNT-2024\u2013017. Approval Date: July 14, 2024. The mice used in the GBM model experiments are SPF-grade, 6\u2009~\u20098\u00a0weeks old, weighing 19\u2009~\u200921\u00a0g, male BALB\/c mice, with a total of 18 mice required. BALB\/c mice are commonly used in GBM pharmacokinetic and biodistribution experiments, and their white fur helps reduce interference with imaging signals. Animal housing: 3\u2009~\u20095 mice per cage. The housing environment is maintained at a temperature of 18\u2009~\u200922\u2103 and relative humidity of 50\u2009~\u200960%. Feeding: Mice are fed a complete nutritional pellet diet. Anesthesia method: Animals are anesthetized with isoflurane. The main measures for animal replacement, reduction in animal use, and reduction in animal suffering and harm include replacing large animals with small animals, reducing the number of animals used, and optimizing experimental protocols.)","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Shengnan Lu, Guangwei He, Ying Li, belongs to a company from Hefei Industrial Pharmaceutical Institute Co., Ltd, Anhui Provincial Key Laboratory of Drug Innovation and Advanced Pharmaceuticals, Hefei 230088, China. The authors have no potential conflicts of interest with the company.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"100"}}