Graphene oxide arms oncolytic measles virus for improved effectiveness of cancer therapy

• Published in: Journal of experimental & clinical cancer research Vol. 38; no. 1; pp. 408 - 16
• Main Authors: Xia, Mao, Luo, Dongjun, Dong, Jie, Zheng, Meihong, Meng, Gang, Wu, Junhua, Wei, Jiwu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18-09-2019; BioMed Central; BMC
• Subjects: A549 Cells; Animals; Antibodies; Antineoplastic agents; Cancer; Cancer cells; Cancer research; Cancer therapies; Cancer treatment; Care and treatment; Delivery vector; Displays (Marketing); Folic acid; Folic Acid - chemistry; Genetic aspects; Genetic vectors; Glycols (Class of compounds); Graphene; Graphene oxide sheets; Graphite; Graphite - chemistry; HeLa Cells; Humans; Male; Measles; Measles virus; Mice; Mice, Nude; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplasms - therapy; Oncolytic measles virus; Oncolytic Virotherapy - methods; Plastic products; Polyethylene glycol; Polyethylene Glycols - chemistry; Polyols; Risk factors; Targeted cancer therapy; Tumors; Virus replication; Xenograft Model Antitumor Assays; Oncolytic measles virus; Graphene oxide sheets; Targeted cancer therapy; Delivery vector
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-019-1410-x

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.
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.
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.
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.