| PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA–docetaxel conjugates |
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| 作者姓名： | Tao Liu Hui Zou Jingqing Mu Xi Zhang Guohua Liu Na Yu Bo Yuan Xiaoyong Yuan Xingjie Liang Shutao Guo |
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| 作者单位： | 1. Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University;2. School of Medicine, Nankai University;3. Clinical College of Ophthalmology, Tianjin Medical University;4. Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital;5. CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences and National Center for Nanoscience and Technology of China |
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| 基金项目： | financially supported by National Natural Science Foundation of China (Nos. 32171386 and 32201157)；;the Natural Science Foundation of Tianjin of China (No. 21JCZDJC01250)；;the China Postdoctoral Science Foundation (No. 2021M690793)； |
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| 摘 要： | Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs, but suffers from poor compatibility between drugs and nanocarriers. Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines. However, the influence of hydrophobic length o...
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| 收稿时间： | 29 September 2022 |
PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA‒docetaxel conjugates |
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| Tao Liu,Hui Zou,Jingqing Mu,Xi Zhang,Guohua Liu,Na Yu,Bo Yuan,Xiaoyong Yuan,Xingjie Liang,Shutao Guo.PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA‒docetaxel conjugates[J].Chinese Chemical Letters,2023,34(9):108135-247. |
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| Institution: | 1. Key Laboratory of Functional Polymer Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China;2. School of Medicine, Nankai University, Tianjin 300071, China;3. Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China;4. Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, China;5. CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences and National Center for Nanoscience and Technology of China, Beijing 100190, China;1. Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325000, China;2. School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325035, China;3. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou 325001, China;4. College of Life and Environmental Science, Wenzhou University, Wenzhou 325000, China;5. College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325000, China;6. National Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210093, China;1. Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing 210096, China;2. Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Key Laboratory of Molecule-Based Materials, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, China;3. Department of Chemistry, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, China;1. Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, Hubei Key Laboratory of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China;2. School of Chemistry and Chemical Engineering, The Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi University, Shihezi 832004, China;3. State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou 730000, China;1. College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China;2. Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education of the People''s Republic of China, Heilongjiang University, Harbin 150080, China;1. Changsha Medical University, Academician Workstation, Changsha 410219, China;2. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China;3. State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Beijing 100850, China;4. Key Laboratory of Biological Nanotechnology of National Health Commission, Changsha 410000, China |
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| Abstract: | Engineering small-molecule drugs into nanoparticulate formulations provides an unprecedented opportunity to improve the performance of traditional chemo drugs, but suffers from poor compatibility between drugs and nanocarriers. Stimuli-responsive mPEG-PDLLA–drug conjugate-based nanomedicines can facilitate the exploitation of beneficial properties of the carrier and enable the practical fabrication of highly efficacious self-assembled nanomedicines. However, the influence of hydrophobic length on the performance of this type of nanomedicine is little known. Here we synthesized two acid-sensitive ketal-linked mPEG-PDLLA–docetaxel prodrugs with different lengths of PDLLA, and engineered them into self-assembled sub-20 nm micellar nanomedicines for breast cancer chemotherapy. We found that the nanomedicine consisting of a mPEG-PDLLA–docetaxel prodrug with the shorter length of PDLLA stood out due to its potent cytotoxicity, deep penetration into multicellular spheroids, and improved in vivo anticancer performance. Additionally, our prodrug-based nanomedicines outperformed the generic formulation of commercial Nanoxel in terms of safety profile, tolerated doses, and tumor suppression. Our findings indicate that the hydrophobic content of a polymeric prodrug nanomedicine plays an important role in the performance of the nanomedicine, and should be instructive for developing polymeric prodrug-based nanomedicines with clinical translational potential. |
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