Delivery of oncolytic adenovirus into the nucleus of tumorigenic cells by tumor microparticles for virotherapy.

Abstract

Oncolytic viruses have been utilized for the treatment of various cancers. However, delivery of the viral particles to tumor cells remains a major challenge. Microparticles (MP) are vesicle forms of plasma membrane fragments of 0.1-1 μm in size that are shed by cells. We have previously shown the delivery of chemotherapeutic drugs using tumor cell-derived MPs (T-MP). Here we report that T-MPs can be utilized as a unique carrier system to deliver oncolytic adenoviruses to human tumors, leading to highly efficient cytolysis of tumor cells needed for in vivo treatment efficacy. This T-MP-mediated oncolytic virotherapy approach holds multiple advantages, including: 1) delivery of oncolytic adenovirus by T-MPs is able to avoid the antiviral effect of host antibodies; 2) delivery of oncolytic adenovirus by T-MPs is not limited by virus-specific receptor that mediates the entry of virus into tumor cells; 3) T-MPs are apt at delivering oncolytic adenoviruses to the nucleus of tumor cells as well as to stem-like tumor-repopulating cells for the desired purpose of killing them. These findings highlight a novel oncolytic adenovirus delivery system with highly promising clinical applications.

• Authors: Li Ran, Xiaohua Tan, Yanchun Li, Huafeng Zhang, Ruihua Ma, Tiantian Ji, Wenqian Dong, Tong Tong, Yuying Liu, Degao Chen, Xiaonan Yin, Xiaoyu Liang, Ke Tang, Jingwei Ma, Yi Zhang, Xuetao Cao, Zhuowei Hu, Xiaofeng Qin, Bo Huang
• Journal: Biomaterials (Biomaterials) Vol. 89 Pg. 56-66 (May 2016) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 26950165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Drug Carriers

Topics

• Adenoviridae (genetics)
• Animals
• Cell Line, Tumor
• Cell-Derived Microparticles (metabolism, pathology)
• Drug Carriers (metabolism)
• Drug Delivery Systems
• Humans
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Neoplasms (genetics, metabolism, pathology, therapy)
• Oncolytic Virotherapy (methods)
• Oncolytic Viruses (genetics)