Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma
Abstract Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing abil...
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202207488 |
| _version_ | 1797797006121369600 |
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| author | Xue Liao Guidong Gong Mengyuan Dai Zhenyu Xiang Jiezhou Pan Xianglian He Jiaojiao Shang Anna Maria Blocki Zongmin Zhao C. Wyatt Shields IV Junling Guo |
| author_facet | Xue Liao Guidong Gong Mengyuan Dai Zhenyu Xiang Jiezhou Pan Xianglian He Jiaojiao Shang Anna Maria Blocki Zongmin Zhao C. Wyatt Shields IV Junling Guo |
| author_sort | Xue Liao |
| collection | DOAJ |
| description | Abstract Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug‐loading with high accumulations in solid tumors. Herein, a tumor‐targeting cellular drug delivery system (MAGN) by surface engineering of tumor‐homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron‐tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the “ON‐OFF” gating effect of the polyphenol‐based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor‐targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs. |
| first_indexed | 2024-03-13T03:41:34Z |
| format | Article |
| id | doaj.art-7555876f10de44d69cef8497b7d0374c |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T03:41:34Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-7555876f10de44d69cef8497b7d0374c2023-06-23T07:34:34ZengWileyAdvanced Science2198-38442023-06-011018n/an/a10.1002/advs.202207488Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic MelanomaXue Liao0Guidong Gong1Mengyuan Dai2Zhenyu Xiang3Jiezhou Pan4Xianglian He5Jiaojiao Shang6Anna Maria Blocki7Zongmin Zhao8C. Wyatt Shields IV9Junling Guo10BMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaBMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaBMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaBMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaBMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaBMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaBMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaSchool of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong Hong Kong SAR 999077ChinaDepartment of Pharmaceutical Sciences College of Pharmacy University of Illinois at Chicago Chicago IL 60612 USADepartment of Chemical and Biological Engineering University of Colorado Boulder CO 80303 USABMI Center for Biomass Materials and Nanointerfaces College of Biomass Science and Engineering Sichuan University Chengdu Sichuan 610065 ChinaAbstract Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug‐loading with high accumulations in solid tumors. Herein, a tumor‐targeting cellular drug delivery system (MAGN) by surface engineering of tumor‐homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron‐tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the “ON‐OFF” gating effect of the polyphenol‐based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor‐targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs.https://doi.org/10.1002/advs.202207488acid‐induced drug releasemacrophagesmetal‐phenolic gatekeepersnanospongestumor‐targeted therapy |
| spellingShingle | Xue Liao Guidong Gong Mengyuan Dai Zhenyu Xiang Jiezhou Pan Xianglian He Jiaojiao Shang Anna Maria Blocki Zongmin Zhao C. Wyatt Shields IV Junling Guo Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma Advanced Science acid‐induced drug release macrophages metal‐phenolic gatekeepers nanosponges tumor‐targeted therapy |
| title | Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma |
| title_full | Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma |
| title_fullStr | Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma |
| title_full_unstemmed | Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma |
| title_short | Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma |
| title_sort | systemic tumor suppression via macrophage driven automated homing of metal phenolic gated nanosponges for metastatic melanoma |
| topic | acid‐induced drug release macrophages metal‐phenolic gatekeepers nanosponges tumor‐targeted therapy |
| url | https://doi.org/10.1002/advs.202207488 |
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