Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy
Glioblastoma (GBM) is one of the most lethal forms of human cancer, with very few long-term survivors. In addition to surgery, chemotherapy is still an important strategy. Unfortunately, GBM chemotherapy faces two main challenges: first, in GBM, epidermal growth factor receptor (EGFR) overexpression...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.921051/full |
| _version_ | 1811292530789056512 |
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| author | Zhen Wang Yuyang Liu Yong Xiao Yandong Xie Ran Wang Yiding Zhang Qi Zhou Liang Liu Shuo Sun Hong Xiao Yuanjie Zou Kun Yang Xiang Li Mengjie Zhao Yifang Hu Hongyi Liu |
| author_facet | Zhen Wang Yuyang Liu Yong Xiao Yandong Xie Ran Wang Yiding Zhang Qi Zhou Liang Liu Shuo Sun Hong Xiao Yuanjie Zou Kun Yang Xiang Li Mengjie Zhao Yifang Hu Hongyi Liu |
| author_sort | Zhen Wang |
| collection | DOAJ |
| description | Glioblastoma (GBM) is one of the most lethal forms of human cancer, with very few long-term survivors. In addition to surgery, chemotherapy is still an important strategy. Unfortunately, GBM chemotherapy faces two main challenges: first, in GBM, epidermal growth factor receptor (EGFR) overexpression results in chemoresistance; second, temozolomide (TMZ) lacks target specificity, which can lead to a reduction in the concentration and side effects in GBM. Nowadays, with the development of nanomedicine systems for applications in tumor therapies, increasing anticancer efficacy and reducing side effects with multi-drug delivery are huge advantages. In this study, pH-sensitive and GBM-targeting nanovesicle (Tf-PEG-PAE(SS)) was fabricated. The chemotherapy drug (TMZ) and EGFR inhibitor (EGFR-siRNA) were co-encapsulated in the nanocarrier, and their anticancer outcomes were investigated in detail. In vitro experiments have shown that the nanocarrier transports TMZ and EGFR-siRNA efficiently into U87 cells, causing a vigorous apoptotic response by silencing the proliferative EGFR gene and increasing the drug concentration of TMZ simultaneously. An experimental study in mice bearing orthotropic glioma revealed that the accumulated nanocarriers in the tumor site could inhibit the tumor growth and prolong the mice survival remarkably through the intracranial injection of Tf-PEG-PAE(SS)/TMZ@siEGFR. The drug co-delivery system could extend the blood circulation time and offer a new strategy to treat glioblastoma. |
| first_indexed | 2024-04-13T04:47:49Z |
| format | Article |
| id | doaj.art-52d4f1d86f554ea280eed403efeb303e |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T04:47:49Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-52d4f1d86f554ea280eed403efeb303e2022-12-22T03:01:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-07-011310.3389/fgene.2022.921051921051Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma TherapyZhen Wang0Yuyang Liu1Yong Xiao2Yandong Xie3Ran Wang4Yiding Zhang5Qi Zhou6Liang Liu7Shuo Sun8Hong Xiao9Yuanjie Zou10Kun Yang11Xiang Li12Mengjie Zhao13Yifang Hu14Hongyi Liu15Department of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neuro-Psychiatric Institute, The Affiliated Brain Hospital with Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Neuro-Psychiatric Institute, The Affiliated Brain Hospital with Nanjing Medical University, Nanjing, ChinaDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital with Nanjing Medical University, Fourth Clinical College of Nanjing Medical University, Nanjing, ChinaGlioblastoma (GBM) is one of the most lethal forms of human cancer, with very few long-term survivors. In addition to surgery, chemotherapy is still an important strategy. Unfortunately, GBM chemotherapy faces two main challenges: first, in GBM, epidermal growth factor receptor (EGFR) overexpression results in chemoresistance; second, temozolomide (TMZ) lacks target specificity, which can lead to a reduction in the concentration and side effects in GBM. Nowadays, with the development of nanomedicine systems for applications in tumor therapies, increasing anticancer efficacy and reducing side effects with multi-drug delivery are huge advantages. In this study, pH-sensitive and GBM-targeting nanovesicle (Tf-PEG-PAE(SS)) was fabricated. The chemotherapy drug (TMZ) and EGFR inhibitor (EGFR-siRNA) were co-encapsulated in the nanocarrier, and their anticancer outcomes were investigated in detail. In vitro experiments have shown that the nanocarrier transports TMZ and EGFR-siRNA efficiently into U87 cells, causing a vigorous apoptotic response by silencing the proliferative EGFR gene and increasing the drug concentration of TMZ simultaneously. An experimental study in mice bearing orthotropic glioma revealed that the accumulated nanocarriers in the tumor site could inhibit the tumor growth and prolong the mice survival remarkably through the intracranial injection of Tf-PEG-PAE(SS)/TMZ@siEGFR. The drug co-delivery system could extend the blood circulation time and offer a new strategy to treat glioblastoma.https://www.frontiersin.org/articles/10.3389/fgene.2022.921051/fullgliomapH-responsive polymeric nanocarriersynergistic therapyTMZsiEGFR |
| spellingShingle | Zhen Wang Yuyang Liu Yong Xiao Yandong Xie Ran Wang Yiding Zhang Qi Zhou Liang Liu Shuo Sun Hong Xiao Yuanjie Zou Kun Yang Xiang Li Mengjie Zhao Yifang Hu Hongyi Liu Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy Frontiers in Genetics glioma pH-responsive polymeric nanocarrier synergistic therapy TMZ siEGFR |
| title | Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy |
| title_full | Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy |
| title_fullStr | Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy |
| title_full_unstemmed | Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy |
| title_short | Intelligent Nanoparticles With pH-Sensitive Co-Delivery of Temozolomide and siEGFR to Ameliorate Glioma Therapy |
| title_sort | intelligent nanoparticles with ph sensitive co delivery of temozolomide and siegfr to ameliorate glioma therapy |
| topic | glioma pH-responsive polymeric nanocarrier synergistic therapy TMZ siEGFR |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.921051/full |
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