Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer
Abstract Background Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle tha...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01738-6 |
| _version_ | 1811188955384643584 |
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| author | Xiao-Yan Yang Jin-Guo Zhang Qiao-Mei Zhou Jie-Ni Yu Yuan-Fei Lu Xiao-Jie Wang Jia-Ping Zhou Xin-Fa Ding Yong-Zhong Du Ri-Sheng Yu |
| author_facet | Xiao-Yan Yang Jin-Guo Zhang Qiao-Mei Zhou Jie-Ni Yu Yuan-Fei Lu Xiao-Jie Wang Jia-Ping Zhou Xin-Fa Ding Yong-Zhong Du Ri-Sheng Yu |
| author_sort | Xiao-Yan Yang |
| collection | DOAJ |
| description | Abstract Background Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. Methods We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. Results Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. Conclusion This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring. Graphical Abstract |
| first_indexed | 2024-04-11T14:27:20Z |
| format | Article |
| id | doaj.art-905e55d320e04433a9bba280b0013776 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T14:27:20Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-905e55d320e04433a9bba280b00137762022-12-22T04:18:48ZengBMCJournal of Nanobiotechnology1477-31552022-12-0120112410.1186/s12951-022-01738-6Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancerXiao-Yan Yang0Jin-Guo Zhang1Qiao-Mei Zhou2Jie-Ni Yu3Yuan-Fei Lu4Xiao-Jie Wang5Jia-Ping Zhou6Xin-Fa Ding7Yong-Zhong Du8Ri-Sheng Yu9Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityInstitute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang UniversityDepartment of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang UniversityAbstract Background Excessive extracellular matrix (ECM) deposition in pancreatic ductal adenocarcinoma (PDAC) severely limits therapeutic drug penetration into tumors and is associated with poor prognosis. Collagen is the most abundant matrix protein in the tumor ECM, which is the main obstacle that severely hinders the diffusion of chemotherapeutic drugs or nanomedicines. Methods We designed a collagenase-functionalized biomimetic drug-loaded Au nanoplatform that combined ECM degradation, active targeting, immune evasion, near-infrared (NIR) light-triggered drug release, and synergistic antitumor therapy and diagnosis into one nanoplatform. PDAC tumor cell membranes were extracted and coated onto doxorubicin (Dox)-loaded Au nanocages, and then collagenase was added to functionalize the cell membrane through lipid insertion. We evaluated the physicochemical properties, in vitro and in vivo targeting, penetration and therapeutic efficacy of the nanoplatform. Results Upon intravenous injection, this nanoplatform efficiently targeted the tumor through the homologous targeting properties of the coated cell membrane. During penetration into the tumor tissue, the dense ECM in the PDAC tissues was gradually degraded by collagenase, leading to a looser ECM structure and deep penetration within the tumor parenchyma. Under NIR irradiation, both photothermal and photodynamic effects were produced and the encapsulated chemotherapeutic drugs were released effectively, exerting a strong synergistic antitumor effect. Moreover, this nanoplatform has X-ray attenuation properties that could serve to guide and monitor treatment by CT imaging. Conclusion This work presented a unique and facile yet effective strategy to modulate ECM components in PDAC, enhance tumor penetration and tumor-killing effects and provide therapeutic guidance and monitoring. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01738-6Tumor penetrationExtracellular matrix degradationBiomimetic membranePhotothermal therapy (PTT)Photodynamic therapy (PDT)CT imaging |
| spellingShingle | Xiao-Yan Yang Jin-Guo Zhang Qiao-Mei Zhou Jie-Ni Yu Yuan-Fei Lu Xiao-Jie Wang Jia-Ping Zhou Xin-Fa Ding Yong-Zhong Du Ri-Sheng Yu Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer Journal of Nanobiotechnology Tumor penetration Extracellular matrix degradation Biomimetic membrane Photothermal therapy (PTT) Photodynamic therapy (PDT) CT imaging |
| title | Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer |
| title_full | Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer |
| title_fullStr | Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer |
| title_full_unstemmed | Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer |
| title_short | Extracellular matrix modulating enzyme functionalized biomimetic Au nanoplatform-mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer |
| title_sort | extracellular matrix modulating enzyme functionalized biomimetic au nanoplatform mediated enhanced tumor penetration and synergistic antitumor therapy for pancreatic cancer |
| topic | Tumor penetration Extracellular matrix degradation Biomimetic membrane Photothermal therapy (PTT) Photodynamic therapy (PDT) CT imaging |
| url | https://doi.org/10.1186/s12951-022-01738-6 |
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