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

Ran L1, Tan X2, Li Y1, Zhang H1, Ma R3, Ji T3, Dong W1, Tong T1, Liu Y1, Chen D1, Yin X1, Liang X1, Tang K1, Ma J1, Zhang Y1, Cao X1, Hu Z4, Qin X5, Huang B6

Biomaterials. 2016 May;89:56-66.
PMID: 26950165  DOI: 10.1016/j.biomaterials.2016.02.025

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.