Citation: Mengxue He, Ling Yu, Yuanyuan Yang, Binhua Zou, Wen Ma, Meng Yu, Jiandong Lu, Guoliang Xiong, Zhiqiang Yu, Aimin Li. Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models[J]. Chinese Chemical Letters, ;2020, 31(12): 3178-3182. doi: 10.1016/j.cclet.2020.05.034 shu

Delivery of triptolide with reduction-sensitive polymer nanoparticles for liver cancer therapy on patient-derived xenografts models

Mengxue He ^{a, 1} ,
Ling Yu ^{b, 1} ,
Yuanyuan Yang ^d ,
Binhua Zou ^d ,
Wen Ma ^d ,
Meng Yu ^d ,
Jiandong Lu ^c ,
Guoliang Xiong ^{c, *,} ,
Zhiqiang Yu ^{d, *,} ,
Aimin Li ^{a, *,}

a.
Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China
b.
Traditional Chinese Medicine Department, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
c.
Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen 518033, China
d.
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China

xiongguoliangzyy@outlook.com

yuzq@smu.edu.cn

liaimin2005@163.com

Received Date: 3 March 2020
Revised Date: 20 May 2020
Accepted Date: 22 May 2020
Available Online: 26 May 2020

Figures(6)

Hepatocellular carcinoma (HCC) has become the fourth predominant cause of cancer-related deaths worldwide, and HCC is still one of the worst prognoses for survival as it is poorly responsive to both chemotherapy and surgical treatment due to drug resistance and great toxic effects. Triptolide (TP), a key ingredient from the traditional Chinese medical herb, has been utilized to treat inflammation and antitumor for centuries. However, investigations of this potent agent have been met with only limited success due to the severe systemic toxicities in patients and low water solubility as well as its high toxicity over the past two decades. Herein, we reported the development of a reduction-responsive drug delivery system loaded with TP for glutathione (GSH)-triggered drug release for cancer therapy. With the GSH-sensitive TP loaded nanoparticles, the remarkable increases in tumor accumulation and amelioration of drug toxicity in animals are demonstrated, which is likely due to sustained stepwise release of active TP within cancer cells. Moreover, in a patient-derived tumor xenograft model of liver cancer, administration of tritolide nanoparticles enhances the antitumor efficacy relative to administration of free TP. These findings indicate that GSH-sensitive release of TP may be a promising strategy for cancer treatment.
- Triptolide,
- Hepatocellular carcinoma,
- Reduction-sensitive polymer,
- Patient-derived xenografts,
- Drug therapy
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