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The rapid clearance and uncontrolled drug release of drug nanocrystals limit their delivery efficiency and clinical application. Herein, an amphiphilic co-polymer, poly oligo(ethylene glycol) methacrylate-b-poly(styrene\u2013co-4-formylphenyl methacrylate) (POEGMA-b-P (St-co-FPMA), PPP), characterized by a hydrophilic part with bottlebrush-like oligo(ethylene glycol) methacrylate (OEGMA) side chains, was synthesized as stabilizers to fabricate a high-drug-loading nanocrystal micelle (053-PPP NC micelle) using the chronic myeloid leukemia (CML) drug candidate N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053 or 053) as a model drug. The 053-PPP NC micelle was characterized and subjected to in vitro and in vivo studies. It featured a worm-like shape of small size, high drug loading (~50%), high colloidal stability, and controlled release in vitro. The presence of the 053-PPP NC micelle resulted in a long-circulation property and a much higher AUC. The 053-PPP NC micelle induced higher accumulation in the tumor tissues under multiple continuous administration. For in vivo efficacy, the 053-PPP NC micelle with a longer dosing interval (96 h), beneficial for improving patient adherence, demonstrated superiority to the 053-F127 NC. The proposed stabilizer PPP and the 053-PPP NC micelle with high drug loading enables drug delivery with long circulation and controlled release of drugs. It is also promising for the development of more efficient nanocrystal-based intravenous injection formulations for poorly water-soluble drugs. It might also offer new possibilities for potential clinical application of the CML candidate drug 053.<\/jats:p>","DOI":"10.3390\/pharmaceutics14081662","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T04:20:32Z","timestamp":1660105232000},"page":"1662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PEG-Bottlebrush Stabilizer-Based Worm-like Nanocrystal Micelles with Long-Circulating and Controlled Release for Delivery of a BCR-ABL Inhibitor against Chronic Myeloid Leukemia (CML)"],"prefix":"10.3390","volume":"14","author":[{"given":"Huamin","family":"Liang","sequence":"first","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengming","family":"Zou","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyi","family":"Fu","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwang","family":"Liu","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beilei","family":"Wang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Liang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9513-3591","authenticated-orcid":false,"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Precision Medicine Research Laboratory of Anhui Province, Hefei 230088, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-2547","authenticated-orcid":false,"given":"Qingsong","family":"Liu","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Precision Medicine Research Laboratory of Anhui Province, Hefei 230088, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106037","DOI":"10.1016\/j.phrs.2021.106037","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update","volume":"175","author":"Roskoski","year":"2022","journal-title":"Pharmacol. 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