Citation: Haotian Shi, Yuchao Luo, Song Zhang, Meijun Zhao, Chaoyong Liu, Qing Pei, Helei Wang, Qiong Dai, Zhigang Xie, Bin Xu, Wenjing Tian. Dual-responsive nanogels with high drug loading for enhanced tumor targeting and treatment[J]. Chinese Chemical Letters, ;2025, 36(10): 110775. doi: 10.1016/j.cclet.2024.110775 shu

Dual-responsive nanogels with high drug loading for enhanced tumor targeting and treatment

Haotian Shi ^{a, e, 1} ,
Yuchao Luo ^{a, f, 1} ,
Song Zhang ^{a, d} ,
Meijun Zhao ^e ,
Chaoyong Liu ^e ,
Qing Pei ^b ,
Helei Wang ^{c, *,} ,
Qiong Dai ^e ,
Zhigang Xie ^{b, *,} ,
Bin Xu ^{a, *,} ,
Wenjing Tian ^a

a.
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China
b.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
c.
Gastric and Intestinal Department, General Surgery Center, First Hospital of Jilin University, Changchun 130021, China
d.
Research Center for Life Science Computing, Zhejiang Lab, Hangzhou 311100, China
e.
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China
f.
School of Mechanical Science and Aerospace Engineering, Jilin University, Changchun 130022, China

helei@jlu.edu.cn

xiez@ciac.ac.cn

xubin@jlu.edu.cn

Received Date: 18 October 2024
Revised Date: 7 December 2024
Accepted Date: 17 December 2024
Available Online: 20 December 2024

Figures(6)

Nanomedicine holds considerable promise for advancing cancer therapy, however, effective delivery of drugs to solid tumors remains a challenge due to rapid systemic clearance and inefficient cellular uptake. Herein, we have developed a novel charge-reversible nanogel to deliver paclitaxel (PTX) dimers (DPP) with enhanced stability and targeting precision. The nanogels exhibit a dynamic charge-reversal mechanism responsive to the acidic tumor microenvironment (TME), optimizing the cellular uptake of prodrugs. In the high glutathione (GSH) conditions within cancer cells, the disulfide bonds in the DPP are cleaved, resulting in the intracellular release of active PTX and reduced drug toxicity to normal cells. In vivo pharmacokinetic studies revealed an extended plasma elimination half-life for the charge-reversible nanocarriers, and antitumor efficacy studies demonstrated superior tumor suppression with minimal systemic toxicity. This research underscores the potential of integrating charge-reversal and responsive release mechanisms into one nanocarrier system, balancing the long circulation and high tumor cell internalization capacity of the nanocarrier, and providing a promising strategy for targeted delivery of nanomedicine.
- Drug delivery,
- Nanogel,
- Charge-reversal,
- Dimeric prodrug,
- Tumor targeting
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