Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects
IntroductionCisplatin (DDP), a platinum-based chemotherapy drug, shows broad antineoplastic activity, however, its clinical use is limited by dose-dependent nephrotoxicity, a major challenge in cancer therapy. The purpose of this study was to investigate the mechanism by which quercetin-polyethylene...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1590688/full |
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| author | Tangna Hao Tangna Hao Tangna Hao Xiaokui Huo Zhen Li Changyuan Wang Changyuan Wang Sha Wu Anni Song Fengyu Zhang Kexin Liu Kexin Liu Kexin Liu |
| author_facet | Tangna Hao Tangna Hao Tangna Hao Xiaokui Huo Zhen Li Changyuan Wang Changyuan Wang Sha Wu Anni Song Fengyu Zhang Kexin Liu Kexin Liu Kexin Liu |
| author_sort | Tangna Hao |
| collection | DOAJ |
| description | IntroductionCisplatin (DDP), a platinum-based chemotherapy drug, shows broad antineoplastic activity, however, its clinical use is limited by dose-dependent nephrotoxicity, a major challenge in cancer therapy. The purpose of this study was to investigate the mechanism by which quercetin-polyethylene glycol-polycaprolactone (Que-PEG-PCL) micelles simultaneously enhance the cytotoxicity of DDP against cancer cells and reduce its nephrotoxicity.MethodsRodent models and HEK293 cells were used to evaluate the renoprotective effects of Que-PEG-PCL micelles. Pharmacokinetics focused on OCT2-mediated renal DDP disposition. Antitumor activity was assessed in CT26 cells and syngeneic tumors. Key assessments included oxidative stress, apoptosis, renal markers, and histopathology.Results:Que-PEG-PCL reduced DDP-induced nephrotoxicity, lowering creatinine and BUN to 42% and 38%. It also reduced oxidative stress and improved antioxidant activity. DDP plasma exposure increased to 323%, with renal clearance reduced to 14%, due to OCT2 inhibition. In a CT26 syngeneic model, combination therapy inhibited tumor volume by 84% compared to control group.DiscussionQue-PEG-PCL enhanced DDP’s therapeutic window by limiting renal accumulation and promoting tumor cell apoptosis. This dual-action strategy provides a novel approach for improving the clinical efficacy of DDP-based cancer therapy. |
| format | Article |
| id | doaj-art-cffb62caf14743148cd3e0d3b46c15b0 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-cffb62caf14743148cd3e0d3b46c15b02025-08-20T03:25:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15906881590688Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effectsTangna Hao0Tangna Hao1Tangna Hao2Xiaokui Huo3Zhen Li4Changyuan Wang5Changyuan Wang6Sha Wu7Anni Song8Fengyu Zhang9Kexin Liu10Kexin Liu11Kexin Liu12Institute of Integrative Medicine, Dalian Medical University, Dalian, ChinaProvincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, ChinaPharmaceutical Research Center, Second Affiliated Hospital, Dalian Medical University, Dalian, ChinaCollege of Pharmacy, Dalian Medical University, Dalian, ChinaProvincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, ChinaDepartment of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Dalian Medical University, Dalian, ChinaInstitute of Integrative Medicine, Dalian Medical University, Dalian, ChinaProvincial Key Laboratory for Pharmacokinetics and Transport, Liaoning Dalian Medical University, Dalian, ChinaDepartment of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, ChinaIntroductionCisplatin (DDP), a platinum-based chemotherapy drug, shows broad antineoplastic activity, however, its clinical use is limited by dose-dependent nephrotoxicity, a major challenge in cancer therapy. The purpose of this study was to investigate the mechanism by which quercetin-polyethylene glycol-polycaprolactone (Que-PEG-PCL) micelles simultaneously enhance the cytotoxicity of DDP against cancer cells and reduce its nephrotoxicity.MethodsRodent models and HEK293 cells were used to evaluate the renoprotective effects of Que-PEG-PCL micelles. Pharmacokinetics focused on OCT2-mediated renal DDP disposition. Antitumor activity was assessed in CT26 cells and syngeneic tumors. Key assessments included oxidative stress, apoptosis, renal markers, and histopathology.Results:Que-PEG-PCL reduced DDP-induced nephrotoxicity, lowering creatinine and BUN to 42% and 38%. It also reduced oxidative stress and improved antioxidant activity. DDP plasma exposure increased to 323%, with renal clearance reduced to 14%, due to OCT2 inhibition. In a CT26 syngeneic model, combination therapy inhibited tumor volume by 84% compared to control group.DiscussionQue-PEG-PCL enhanced DDP’s therapeutic window by limiting renal accumulation and promoting tumor cell apoptosis. This dual-action strategy provides a novel approach for improving the clinical efficacy of DDP-based cancer therapy.https://www.frontiersin.org/articles/10.3389/fphar.2025.1590688/fullcisplatinnephrotoxicityquercetinpolymeric micellesantitumor potency |
| spellingShingle | Tangna Hao Tangna Hao Tangna Hao Xiaokui Huo Zhen Li Changyuan Wang Changyuan Wang Sha Wu Anni Song Fengyu Zhang Kexin Liu Kexin Liu Kexin Liu Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects Frontiers in Pharmacology cisplatin nephrotoxicity quercetin polymeric micelles antitumor potency |
| title | Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects |
| title_full | Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects |
| title_fullStr | Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects |
| title_full_unstemmed | Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects |
| title_short | Molecular pharmacokinetic mechanism of quercetin-encapsulated polymeric micelles in alleviating cisplatin-induced nephrotoxicity and enhancing antineoplastic effects |
| title_sort | molecular pharmacokinetic mechanism of quercetin encapsulated polymeric micelles in alleviating cisplatin induced nephrotoxicity and enhancing antineoplastic effects |
| topic | cisplatin nephrotoxicity quercetin polymeric micelles antitumor potency |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1590688/full |
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