Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain

ABSTRACT Postoperative pain and tumor recurrence are critical challenges following malignant tumor resection. To address these issues, we developed a supramolecular gel delivery system loaded with ropivacaine microcrystals (RopC Gel). Using PEG400 as the solvent, we successfully screened and identif...

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Main Authors: Jiangtao Lin, Bin Liu, Quan Wang, Yi Duan, Yijie Qiu, Qi Wu, Qi Wang, Yi Dong, Hao Fu, Xinyue Wang, Yourong Duan
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Aggregate
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Online Access:https://doi.org/10.1002/agt2.734
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author Jiangtao Lin
Bin Liu
Quan Wang
Yi Duan
Yijie Qiu
Qi Wu
Qi Wang
Yi Dong
Hao Fu
Xinyue Wang
Yourong Duan
author_facet Jiangtao Lin
Bin Liu
Quan Wang
Yi Duan
Yijie Qiu
Qi Wu
Qi Wang
Yi Dong
Hao Fu
Xinyue Wang
Yourong Duan
author_sort Jiangtao Lin
collection DOAJ
description ABSTRACT Postoperative pain and tumor recurrence are critical challenges following malignant tumor resection. To address these issues, we developed a supramolecular gel delivery system loaded with ropivacaine microcrystals (RopC Gel). Using PEG400 as the solvent, we successfully screened and identified matrix materials capable of forming supramolecular hydrogels through a heating–cooling process. By strategically leveraging the hydrophilic and hydrophobic properties of the gel matrix, we controlled its mechanical strength and degradation rate by adjusting the ratio of hydrophilic to hydrophobic components, resulting in a degradable, injectable, and self‐healing gel delivery system. In both rat plantar incision and mouse tumor resection pain models, RopC Gel provided long‐lasting analgesia for up to 5 days. Notably, tumor‐resected mice treated with RopC Gel demonstrated extended survival and slower tumor progression. Further in vitro and in vivo experiments revealed that RopC Gel affects mitochondrial function by promoting the accumulation of reactive oxygen species in tumor cells, inducing pyroptosis, stimulating immunogenic cell death (ICD), and activating anti‐tumor immune responses. This work offers an innovative solution for postoperative tumor resection management. Additionally, the controllable degradation properties outlined in this study provide an efficient strategy for the controlled release of multiple drugs, with the potential for widespread clinical applications.
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spelling doaj-art-263e908ab75f4ce4a2d4a5e863b317f02025-08-20T02:27:28ZengWileyAggregate2692-45602025-04-0164n/an/a10.1002/agt2.734Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative PainJiangtao Lin0Bin Liu1Quan Wang2Yi Duan3Yijie Qiu4Qi Wu5Qi Wang6Yi Dong7Hao Fu8Xinyue Wang9Yourong Duan10State Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChinaState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChinaState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChinaState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChinaDepartment of UltrasoundXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChinaShanghai Key Laboratory of Functional Materials ChemistryKey Laboratory for Advanced Materials and Institute of Fine ChemicalsJoint International Research Laboratory of Precision Chemistry and Molecular EngineeringFeringa Nobel Prize Scientist Joint Research CenterFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChinaShanghai Key Laboratory of Functional Materials ChemistryKey Laboratory for Advanced Materials and Institute of Fine ChemicalsJoint International Research Laboratory of Precision Chemistry and Molecular EngineeringFeringa Nobel Prize Scientist Joint Research CenterFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChinaDepartment of UltrasoundXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene RegulationGuangdong‐Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat‐Sen Memorial HospitalSun Yat‐Sen UniversityGuangzhou ChinaState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChinaState Key Laboratory of Systems Medicine for CancerShanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChinaABSTRACT Postoperative pain and tumor recurrence are critical challenges following malignant tumor resection. To address these issues, we developed a supramolecular gel delivery system loaded with ropivacaine microcrystals (RopC Gel). Using PEG400 as the solvent, we successfully screened and identified matrix materials capable of forming supramolecular hydrogels through a heating–cooling process. By strategically leveraging the hydrophilic and hydrophobic properties of the gel matrix, we controlled its mechanical strength and degradation rate by adjusting the ratio of hydrophilic to hydrophobic components, resulting in a degradable, injectable, and self‐healing gel delivery system. In both rat plantar incision and mouse tumor resection pain models, RopC Gel provided long‐lasting analgesia for up to 5 days. Notably, tumor‐resected mice treated with RopC Gel demonstrated extended survival and slower tumor progression. Further in vitro and in vivo experiments revealed that RopC Gel affects mitochondrial function by promoting the accumulation of reactive oxygen species in tumor cells, inducing pyroptosis, stimulating immunogenic cell death (ICD), and activating anti‐tumor immune responses. This work offers an innovative solution for postoperative tumor resection management. Additionally, the controllable degradation properties outlined in this study provide an efficient strategy for the controlled release of multiple drugs, with the potential for widespread clinical applications.https://doi.org/10.1002/agt2.734long‐acting analgesiapostoperative painpyroptosissupramolecular gelstumor recurrence
spellingShingle Jiangtao Lin
Bin Liu
Quan Wang
Yi Duan
Yijie Qiu
Qi Wu
Qi Wang
Yi Dong
Hao Fu
Xinyue Wang
Yourong Duan
Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain
Aggregate
long‐acting analgesia
postoperative pain
pyroptosis
supramolecular gels
tumor recurrence
title Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain
title_full Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain
title_fullStr Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain
title_full_unstemmed Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain
title_short Supramolecular Gels With Controllable Degradation for Suppressing Tumor Recurrence and Relieving Postoperative Pain
title_sort supramolecular gels with controllable degradation for suppressing tumor recurrence and relieving postoperative pain
topic long‐acting analgesia
postoperative pain
pyroptosis
supramolecular gels
tumor recurrence
url https://doi.org/10.1002/agt2.734
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