Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates
Abstract Numerous reports have demonstrated the construction of supramolecular nanodrugs (SNDs) via the π–π stacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugate units. However, the destruction of π–π stacking and the subsequent dis...
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2025-01-01
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| author | Wenzhe Xu Ruixu Yang Yingke Xue Yang Chen Shuwei Liu Songling Zhang Yonggang Wang Yi Liu Hao Zhang |
| author_facet | Wenzhe Xu Ruixu Yang Yingke Xue Yang Chen Shuwei Liu Songling Zhang Yonggang Wang Yi Liu Hao Zhang |
| author_sort | Wenzhe Xu |
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| description | Abstract Numerous reports have demonstrated the construction of supramolecular nanodrugs (SNDs) via the π–π stacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugate units. However, the destruction of π–π stacking and the subsequent disassembly of SNDs under tumor microenvironment (TME), which is the precondition for drug release, have not been clearly described. In this work, based on a disassembly model of π–π stacked naphthoquinone SNDs, the influence of co‐assembled drugs on disassembly is delineated. Both the experimental observation and computational simulation indicate that the disassembly of SNDs under simulated TME highly depends on the disassembly activation energy (ΔEdis) of neighboring π–π stacked molecules. Owing to the high ΔEdis, the disassembly of self‐assembled naphthoquinone SNDs is greatly restricted. Meaningfully, the ΔEdis is the sum of a series of activation energy according to the specific stimuli of TME. Thus, a concept of stimuli‐responsive drug‐mates is proposed for boosting the disassembly of π–π stacked SNDs, namely the foremost co‐assembly of π‐conjugated drugs with additional drug molecules that possess relatively weak π–π interaction but high TME responsiveness. Further computational simulation reveals that the introduction of stimuli‐responsive drug‐mates significantly lowers the ΔEdis, thus accelerating the disassembly of SNDs and the release of drug payloads. Holding the advantages of π‐conjugated drug library, the concept of stimuli‐responsive drug‐mates gives an extensive design of π–π stacked SNDs toward heterogeneous nidus microenvironment responsiveness, which highlights the superiority of widely used drug co‐assembly strategy in constructing multifunctional SNDs. |
| format | Article |
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| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-26671479b55640eb9453540776c2a1b92025-01-21T08:57:07ZengWileyAggregate2692-45602025-01-0161n/an/a10.1002/agt2.648Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐matesWenzhe Xu0Ruixu Yang1Yingke Xue2Yang Chen3Shuwei Liu4Songling Zhang5Yonggang Wang6Yi Liu7Hao Zhang8State Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun P. R. ChinaState Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun P. R. ChinaState Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun P. R. ChinaState Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun P. R. ChinaJoint Laboratory of Opto‐Functional Theranostics in Medicine and Chemistry Institute of Translational Medicine The First Hospital of Jilin University Changchun P. R. ChinaDepartment of Gynecological Oncology Gynecology and Obstetrics Center The First Hospital of Jilin University Changchun P. R. ChinaDepartment of Cardiovascular Centre The First Hospital of Jilin University Changchun P. R. ChinaState Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun P. R. ChinaState Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun P. R. ChinaAbstract Numerous reports have demonstrated the construction of supramolecular nanodrugs (SNDs) via the π–π stacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugate units. However, the destruction of π–π stacking and the subsequent disassembly of SNDs under tumor microenvironment (TME), which is the precondition for drug release, have not been clearly described. In this work, based on a disassembly model of π–π stacked naphthoquinone SNDs, the influence of co‐assembled drugs on disassembly is delineated. Both the experimental observation and computational simulation indicate that the disassembly of SNDs under simulated TME highly depends on the disassembly activation energy (ΔEdis) of neighboring π–π stacked molecules. Owing to the high ΔEdis, the disassembly of self‐assembled naphthoquinone SNDs is greatly restricted. Meaningfully, the ΔEdis is the sum of a series of activation energy according to the specific stimuli of TME. Thus, a concept of stimuli‐responsive drug‐mates is proposed for boosting the disassembly of π–π stacked SNDs, namely the foremost co‐assembly of π‐conjugated drugs with additional drug molecules that possess relatively weak π–π interaction but high TME responsiveness. Further computational simulation reveals that the introduction of stimuli‐responsive drug‐mates significantly lowers the ΔEdis, thus accelerating the disassembly of SNDs and the release of drug payloads. Holding the advantages of π‐conjugated drug library, the concept of stimuli‐responsive drug‐mates gives an extensive design of π–π stacked SNDs toward heterogeneous nidus microenvironment responsiveness, which highlights the superiority of widely used drug co‐assembly strategy in constructing multifunctional SNDs.https://doi.org/10.1002/agt2.648disassemblydrug releasenaphthoquinonesstimuli‐responsive drug‐matessupramolecular nanodrugsπ–π stacking |
| spellingShingle | Wenzhe Xu Ruixu Yang Yingke Xue Yang Chen Shuwei Liu Songling Zhang Yonggang Wang Yi Liu Hao Zhang Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates Aggregate disassembly drug release naphthoquinones stimuli‐responsive drug‐mates supramolecular nanodrugs π–π stacking |
| title | Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates |
| title_full | Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates |
| title_fullStr | Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates |
| title_full_unstemmed | Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates |
| title_short | Boosting disassembly of π–π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli‐responsive drug‐mates |
| title_sort | boosting disassembly of π π stacked supramolecular nanodrugs under tumor microenvironment by introducing stimuli responsive drug mates |
| topic | disassembly drug release naphthoquinones stimuli‐responsive drug‐mates supramolecular nanodrugs π–π stacking |
| url | https://doi.org/10.1002/agt2.648 |
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