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Chongqing","award":["2023-23-14"],"award-info":[{"award-number":["2023-23-14"]}]},{"name":"Chongging Municipal Science and Technology Bureau Chongqing Special Major Project for Technological Innovation and Application Development of Chongqing","award":["CSTB2024TIAD-STX0041"],"award-info":[{"award-number":["CSTB2024TIAD-STX0041"]}]},{"name":"Chongging Municipal Science and Technology Bureau Chongqing Special Major Project for Technological Innovation and Application Development of Chongqing","award":["cstc2024ycjh-bgzxm0111"],"award-info":[{"award-number":["cstc2024ycjh-bgzxm0111"]}]},{"name":"Chongqing municipal talent plan \u201cLump sum project\u201d of Chongqing Science and Technology Bureau","award":["KJQN 202315137"],"award-info":[{"award-number":["KJQN 202315137"]}]},{"name":"Chongqing municipal talent plan \u201cLump sum project\u201d of Chongqing Science and Technology Bureau","award":["CSTB2024NSCQ-MSX1086"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX1086"]}]},{"name":"Chongqing municipal talent plan \u201cLump sum project\u201d of Chongqing Science and Technology Bureau","award":["2023-23-14"],"award-info":[{"award-number":["2023-23-14"]}]},{"name":"Chongqing municipal talent plan \u201cLump sum project\u201d of Chongqing Science and Technology Bureau","award":["CSTB2024TIAD-STX0041"],"award-info":[{"award-number":["CSTB2024TIAD-STX0041"]}]},{"name":"Chongqing municipal talent plan \u201cLump sum project\u201d of Chongqing Science and Technology Bureau","award":["cstc2024ycjh-bgzxm0111"],"award-info":[{"award-number":["cstc2024ycjh-bgzxm0111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Based on our previous study, Celastrol-based proteolysis-targeting chimeras (Celastrol-PROTACs) were shown to induce apoptosis in 4T1 cells by selectively degrading GRP94 and CDK1\/4 through the endogenous ubiquitin\u2013proteasome system. However, their clinical translation is limited by poor solubility, low targeting efficiency, and liver and kidney toxicity. Methods: To address these limitations, we developed a pegylated liposomal formulation of Celastrol-PROTACs (Lip-Celastrol-PROTACs) and evaluated its therapeutic efficacy and safety profile. Results: The tumor volume of the mice in the Celastrol-PROTACs solution group (286 \u00b1 79 mm3) was significantly larger than that of those in the Lip-Celastrol-PROTACs group (229 \u00b1 49 mm3) on day 18 after intravenous administration (p &lt; 0.01). This difference between the two groups was statistically significant (p &lt; 0.01). Notably, the Celastrol-PROTACs group exhibited significantly greater weight loss compared to the Lip-Celastrol-PROTACs group (p &lt; 0.001). In vivo toxicity assessments revealed that the levels of AST and BUN in the Celastrol-PROTACs group were 27.93 \u00b1 4.88 U\/L and 12.36 \u00b1 1.33 \u03bcmol\/L, respectively, whereas those in the Lip-Celastrol-PROTACs group were found to be 7.92 \u00b1 0.94 U\/L and 8.19 \u00b1 0.67 \u03bcmol\/L, respectively. These findings indicate a statistically significant difference between the two formulations (p &lt; 0.01). Conclusions: Our research demonstrated that pegylated liposomes could improve the targeting efficiency and minimize the toxicity of PROTACs, thereby improving overall therapeutic efficacy. These findings indicated that Lip-Celastrol-PROTACs represent a promising strategy for future clinical applications.<\/jats:p>","DOI":"10.3390\/ph18091381","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T11:19:31Z","timestamp":1758021571000},"page":"1381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development and Evaluation of Liposomal Celastrol-PROTACs for Treating Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Xuebin","family":"Li","sequence":"first","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Yu","sequence":"additional","affiliation":[{"name":"Research Center of Pharmaceutical Preparations and Nanomedicine, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gongyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghong","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China"},{"name":"College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing 402760, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/cncr.28914","article-title":"Subtyping of triple-negative breast cancer: Implications for therapy","volume":"121","author":"Abramson","year":"2015","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1634\/theoncologist.2014-0002","article-title":"Measures of outcome in metastatic breast cancer: Insights from a real-world scenario","volume":"19","author":"Bonotto","year":"2014","journal-title":"Oncologist"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/CM9.0000000000001474","article-title":"Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020","volume":"134","author":"Cao","year":"2021","journal-title":"Chin. 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