中国化学快报(英文版)2024，Vol.35Issue(4) ：280-286.DOI:10.1016/j.cclet.2023.108656

Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin(Ⅳ)prodrug delivery and enhanced colorectal cancer therapy

Wenjia Wang Xingyue He Xiaojie Wang Tiantian Zhao Osamu Muraoka Genzoh Tanabe Weijia Xie Tianjiao Zhou Lei Xing Qingri Jin Hulin Jiang
中国化学快报(英文版)2024，Vol.35Issue(4) ：280-286.DOI:10.1016/j.cclet.2023.108656
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Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin(Ⅳ)prodrug delivery and enhanced colorectal cancer therapy

Wenjia Wang 1Xingyue He 1Xiaojie Wang 1Tiantian Zhao 1Osamu Muraoka 2Genzoh Tanabe 2Weijia Xie 3Tianjiao Zhou 1Lei Xing 1Qingri Jin 4Hulin Jiang5
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作者信息

  • 1. State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China
  • 2. Faculty of Pharmacy Kinki University,Higashiosaka,Osaka 577-8502,Japan
  • 3. State Key Laboratory of Natural Medicines(SKLNM)and Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China
  • 4. School of Pharmacy,Hangzhou Medical College,Hangzhou 311399,China
  • 5. State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China;College of Pharmacy,Yanbian University,Yanji 133002,China
  • 折叠

Abstract

Oxaliplatin(Oxa)is the first-line chemotherapeutic drug for the treatment of colorectal cancer(CRC).However,long-term Oxa chemotherapy can induce inflammation and increase the levels of cyclooxygenase-2(COX-2)and prostaglandin E2(PGE2),which can promote tumor metastasis.Moreover,high glutathione(GSH)levels in CRC cells significantly reduce Oxa sensitivity and seriously restrict the clinical application of Oxa.Herein,an Oxa(Ⅳ)prodrug with anti-inflammatory properties(desmethyl naproxe,DN)and GSH-depleting cyclodextrin pseudo-polyrotaxane carriers were prepared and further self-assembled into micellar nanoparticles(designated DNPt@PPRI).The relesae of DN from DNPt@PPRI can reduce the level of PGE2 to inhibit inflammation and tumor metastasis by decreasing COX-2 protein,and also synergize with Oxa to inhibit tumor.More importantly,GSH depletion can reduce the detoxifi-cation of Oxa and further enhance chemotherapy-induced apoptosis.DNPt@PPRI have a good GSH deple-tion ability to enhance the sensitivity of Oxa,indicating a potential in the synergistic chemotherapy and chemo-sensitization of colorectal cancer.

Key words

Oxaliplatin/Glutathione depletion/Tetravalent platinum prodrug/Synergistic therapy/Colorectal cancer

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基金项目

国家自然科学基金(82020108029)

国家自然科学基金(82073398)

Priority Academic Program Devel-opment of Jiangsu Higher Education Institutions()

Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202021)

高等学校学科创新引智计划(111计划)()

State Administration of Foreign Ex-perts Affairs of China(B16046)

Double First-Rate construc-tion plan of China Pharmaceutical University(CPU2018GY06)

Double First-Rate construc-tion plan of China Pharmaceutical University(CPU2022QZ18)

中国博士后科学基金(2021M703598)

中国博士后科学基金(2022M720173)

Jiangsu Funding Program for Excel-lent Postdoctoral Talent and International Postdoctoral Exchange Fellowship Program(2022)()

出版年

2024
中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCDCSCD
影响因子：0.771
ISSN：1001-8417
参考文献量61
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