| At present, the chemotherapy, radiotherapy and the surgery are still playing a leading role in treating tumors. Biotherapy is showing huge potential with the development of molecular biology for last few decades. Oncolytic virotherapy is currently developed by genetically modifying viruses for their selective infection and destruction of cancer cells, in which the oncolytic adenovirus (OA) is invested high expectations for its relative safety. However, like all oncolytic viruses, systemic administration of OA will make it susceptible to inactivation by pre-existing antibodies in patients and lead to treatment failure. As a result, a number of biological vectors, such as mesenchymal stem cells, myeloid-derived suppressor cells, cytokine-induced killer cells, etc., have been used to deliver OA. But their clinical use is restricted due to the side effects.Based on previous research results of our team in which we found that T-MPs can deliver chemotherapy drugs to tumor cells and kill these cells. But whether T-MPs can act as the vector for delivering OA is still poor known. Considering the diameter of OA is about 90-100 nm which is much smaller than that of T-MPs (700-800 nm), we assumed that the T-MPs might also wrap the OA particles and perform as an OA delivery carrier to kill tumor cells.Therefore, this study mainly focused on three parts as described below.1. Detected whether T-MPs could act as OA carrier.We used A549 cells for producing T-MPs. Identified the typical shape of T-MPs by electron microscope, and their diameter by flow cytometry and particle size distribution analysis; then we confirmed the OA’s exist using two-photon microscope, and PCR.2. Examined whether OA-MPs could kill tumor cells.OA-MPs were co-cultured with several kinds of tumor cells in vitro and the cells’ states were observed. Besides, OA-MPs were injected subcutaneously or intraperitoneally to the tumor-bearing nude mice. The volume and weight of the tumor from all groups were measured and the long term survival of these mice was also recorded for comparison. The results showed that OA-MPs could kill tumor cells effectively.3. The advantages of OA-MPs treatment over OA treatment.The tumoricidal effect of OA-MPs was checked to compare with OA using both in vivo and in vitro experiments. We found that OA-MPs have the following unique advantages:OA-MPs could protect OA from the recognition and clearance of specific neutralizing antibodies; OA-MPs could mediate the nucleic entry of OA faster than that using OA alone; Unlike OA, which enters the tumor cell mainly depending on the coxsackievirus and adenovirus receptor (CAR), OA-MPs acted through an entire CAR-independent way. So if the CAR’s expression is down-regulated or even shut off, OA-MPs’ function will not be influenced; OA-MPs could inhibit the stem-like tumor-repopulating cells in 3D culture system more efficiently than OA.In this study, we presented a new biological carrier, T-MPs, for delivering OA to kill tumor cells. This acellular tool has significant advantages when compared with OA and other control in vitro and in vivo experiments. So it seems that OA-MPs’ therapeutic advantages might shed some light on their potential clinical application. Nevertheless, this study is just a tip of the iceberg for OA-MPs, further researchesare needed in the future.
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