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

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

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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.

OxaliplatinGlutathione depletionTetravalent platinum prodrugSynergistic therapyColorectal cancer

Wenjia Wang、Xingyue He、Xiaojie Wang、Tiantian Zhao、Osamu Muraoka、Genzoh Tanabe、Weijia Xie、Tianjiao Zhou、Lei Xing、Qingri Jin、Hulin Jiang

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State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 210009,China

Faculty of Pharmacy Kinki University,Higashiosaka,Osaka 577-8502,Japan

State Key Laboratory of Natural Medicines(SKLNM)and Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China

School of Pharmacy,Hangzhou Medical College,Hangzhou 311399,China

College of Pharmacy,Yanbian University,Yanji 133002,China

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国家自然科学基金国家自然科学基金Priority Academic Program Devel-opment of Jiangsu Higher Education InstitutionsProject of State Key Laboratory of Natural Medicines,China Pharmaceutical University高等学校学科创新引智计划(111计划)State Administration of Foreign Ex-perts Affairs of ChinaDouble First-Rate construc-tion plan of China Pharmaceutical UniversityDouble First-Rate construc-tion plan of China Pharmaceutical University中国博士后科学基金中国博士后科学基金Jiangsu Funding Program for Excel-lent Postdoctoral Talent and International Postdoctoral Exchange Fellowship Program(2022)

8202010802982073398SKLNMZZ202021B16046CPU2018GY06CPU2022QZ182021M7035982022M720173

2024

10.1016/j.cclet.2023.108656

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(4)
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