Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy
Abstract Background Replication-competent oncolytic viruses (OVs) have been proven to be a potent anticancer weapon for clinical therapy. The preexisting neutralizing antibody in patients is a big challenge for oncolytic efficacy of OVs. Graphene oxide sheets (GOS) possess excellent biological compa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1410-x |
| _version_ | 1819161971936722944 |
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| author | Mao Xia Dongjun Luo Jie Dong Meihong Zheng Gang Meng Junhua Wu Jiwu Wei |
| author_facet | Mao Xia Dongjun Luo Jie Dong Meihong Zheng Gang Meng Junhua Wu Jiwu Wei |
| author_sort | Mao Xia |
| collection | DOAJ |
| description | Abstract Background Replication-competent oncolytic viruses (OVs) have been proven to be a potent anticancer weapon for clinical therapy. The preexisting neutralizing antibody in patients is a big challenge for oncolytic efficacy of OVs. Graphene oxide sheets (GOS) possess excellent biological compatibility and are easy to decorate for targeted delivery. Methods We generated PEI-GOS-PEG-FA (Polyethyleneimine-Graphene oxide sheets-Polyethylene glycol-Folic acid). After intravenous injection, the distribution of PEI-GOS-PEG-FA in tumor-bearing mice was visualized by the IVIS Lumina XR system. Then, the oncolytic measles virus (MV-Edm) was coated with PEI-GOS-PEG-FA to form a viral-GOS complex (GOS/MV-Edm). The oncolytic effects of GOS/MV-Edm were investigated both in vitro and in vivo. Results GOS/MV-Edm exhibited higher infectivity and enhanced oncolysis. In tumor-bearing mice, GOS/MV-Edm had significantly elevated viral replication within the tumor mass, and achieved an improved antitumor effect. Then, we confirmed that GOS/MV-Edm entered cancer cells via the folate receptor instead of CD46, a natural cognate receptor of MV-Edm. GOS/MV-Edm remained the infectivity in murine cells that lack CD46. Finally, we found that GOS/MV-Edm was effectively protected from neutralization in the presence of antiserum both in vitro and in vivo. In passively antiserum immunized tumor-bearing mice, the survival was remarkably improved with intravenous injection of GOS/MV-Edm. Conclusion Our findings demonstrate that GOS/MV-Edm displays significantly elevated viral replication within the tumor mass, leading to an improved antitumor effect in solid tumor mouse model. Our study provided a novel strategy to arm OVs for more efficient cancer therapy. That may become a promising therapeutic strategy for cancer patients. |
| first_indexed | 2024-12-22T17:20:50Z |
| format | Article |
| id | doaj.art-f780af9a0d75458ab806f3e3697b0cfe |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-22T17:20:50Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-f780af9a0d75458ab806f3e3697b0cfe2022-12-21T18:18:50ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-09-0138111610.1186/s13046-019-1410-xGraphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapyMao Xia0Dongjun Luo1Jie Dong2Meihong Zheng3Gang Meng4Junhua Wu5Jiwu Wei6Department of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing UniversityJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing UniversityThe Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing UniversityJiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing UniversityAbstract Background Replication-competent oncolytic viruses (OVs) have been proven to be a potent anticancer weapon for clinical therapy. The preexisting neutralizing antibody in patients is a big challenge for oncolytic efficacy of OVs. Graphene oxide sheets (GOS) possess excellent biological compatibility and are easy to decorate for targeted delivery. Methods We generated PEI-GOS-PEG-FA (Polyethyleneimine-Graphene oxide sheets-Polyethylene glycol-Folic acid). After intravenous injection, the distribution of PEI-GOS-PEG-FA in tumor-bearing mice was visualized by the IVIS Lumina XR system. Then, the oncolytic measles virus (MV-Edm) was coated with PEI-GOS-PEG-FA to form a viral-GOS complex (GOS/MV-Edm). The oncolytic effects of GOS/MV-Edm were investigated both in vitro and in vivo. Results GOS/MV-Edm exhibited higher infectivity and enhanced oncolysis. In tumor-bearing mice, GOS/MV-Edm had significantly elevated viral replication within the tumor mass, and achieved an improved antitumor effect. Then, we confirmed that GOS/MV-Edm entered cancer cells via the folate receptor instead of CD46, a natural cognate receptor of MV-Edm. GOS/MV-Edm remained the infectivity in murine cells that lack CD46. Finally, we found that GOS/MV-Edm was effectively protected from neutralization in the presence of antiserum both in vitro and in vivo. In passively antiserum immunized tumor-bearing mice, the survival was remarkably improved with intravenous injection of GOS/MV-Edm. Conclusion Our findings demonstrate that GOS/MV-Edm displays significantly elevated viral replication within the tumor mass, leading to an improved antitumor effect in solid tumor mouse model. Our study provided a novel strategy to arm OVs for more efficient cancer therapy. That may become a promising therapeutic strategy for cancer patients.http://link.springer.com/article/10.1186/s13046-019-1410-xOncolytic measles virusDelivery vectorGraphene oxide sheetsTargeted cancer therapy |
| spellingShingle | Mao Xia Dongjun Luo Jie Dong Meihong Zheng Gang Meng Junhua Wu Jiwu Wei Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy Journal of Experimental & Clinical Cancer Research Oncolytic measles virus Delivery vector Graphene oxide sheets Targeted cancer therapy |
| title | Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy |
| title_full | Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy |
| title_fullStr | Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy |
| title_full_unstemmed | Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy |
| title_short | Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy |
| title_sort | graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy |
| topic | Oncolytic measles virus Delivery vector Graphene oxide sheets Targeted cancer therapy |
| url | http://link.springer.com/article/10.1186/s13046-019-1410-x |
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