Citation: 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. doi: 10.1016/j.cclet.2023.108135 shu

PDLLA length on anti-breast cancer efficacy of acid-responsive self-assembling mPEG-PDLLA‒docetaxel conjugates

Tao Liu ^{a, 1} ,
Hui Zou ^{a, 1} ,
Jingqing Mu ^a ,
Xi Zhang ^a ,
Guohua Liu ^a ,
Na Yu ^a ,
Bo Yuan ^b ,
Xiaoyong Yuan ^{b, c, d, *,} ,
Xingjie Liang ^e ,
Shutao Guo ^{a, *,}

a.
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
b.
School of Medicine, Nankai University, Tianjin 300071, China
c.
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin 300020, China
d.
Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin Eye Hospital, Tianjin 300020, China
e.
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

yuanxy_cn@hotmail.com

stguo@nankai.edu.cn

Received Date: 29 September 2022
Revised Date: 29 December 2022
Accepted Date: 3 January 2023
Available Online: 5 January 2023

Figures(4)

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.
- Nanomedicine,
- Prodrug,
- Docetaxel,
- mPEG-PDLLA,
- Acid-sensitive
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