Nanotechnology and nano-sized tools: Newer approaches to circumvent oncolytic adenovirus limitations.

Oncolytic adenoviruses (OAds), engineered Ads preferentially infect and lyse tumor cells, have attracted remarkable attention as immunotherapy weapons for the treatment of various malignancies. Despite hopeful successes in preclinical investigations and translation into clinical phases, they face some challenges that thwart their therapeutic effectiveness, including low infectivity of cancer cells, liver sequestration, pre-existing neutralizing antibodies, physical barriers to the spread of Ads, and immunosuppressive TME. Nanotechnology and nano-sized tools provide several advantages to overcome these limitations of OAds. Nano-sized tools could improve the therapeutic efficacy of OAds by enhancing infectivity and cellular uptake, targeting and protecting from pre-existing immune responses, masking and preventing liver tropism, and co-delivery with other therapeutic agents. Herein, we reviewed the constructs of various OAds and their application in clinical trials, as well as the limitations they have faced. Furthermore, we emphasized the potential applications of nanotechnology to solve the constraints of OAds to improve their anti-tumor activities.

Platelet storage media change the expression characteristics of the platelet-derived microparticles.

Activated platelets shed microparticles in vivo and definitely in vitro upon aging under storage. Studies about the platelet-derived microparticles (PMPs) produced in different storage media of PC were very limited. The aim of this research was to compare some surface molecules of these microvesicles in dissimilar microenvironments; plasma and the candidate medium for the platelet concentrate, Composol. Thirty units of PCs were prepared from Iranian Blood Transfusion Organization. Each unit was divided into two portions. In one of the portions, plasma was replaced with Composol using a connecting device instrument. MPs were isolated from PC and the levels of PS exposure (the annexin-binding capacity) and binding to vWF were surveyed on their surface using ELISA and flow cytometry techniques. The levels of PS exposure were increased on MPs during 7 days storage in the both media but the differences were not significant (P value >0.05). In addition, binding of PMP to vWF was declined during storage. The binding capabilities of PMP were significantly higher in Composol than that of plasma at the day 4 or 7 of storage (P value = 001). It seemed that the binding of PMPs to vWF was affected from the storage media of PC (plasma and Composol) but PS exposure was not affected from the type of storage media.

The caspase-3 inhibitor (peptide Z-DEVD-FMK) affects the survival and function of platelets in platelet concentrate during storage.

BACKGROUND: Although apoptosis occurs in nucleated cells, studies show that this event also occurs in some anucleated cells such as platelets. During storage of platelets, the viability of platelets decreased, storage lesions were observed, and cells underwent apoptosis. We investigated the effects of caspase-3 inhibitor on the survival and function of platelets after different periods of storage. METHODS: Platelet concentrates were obtained from the Iranian Blood Transfusion Organization in plastic blood bags. Caspase-3 inhibitor (Z-DEVD-FMK) was added to the bags. These bags along with control bags to which no inhibitor was added were stored in a shaking incubator at 22℃ for 7 days. The effects of Z-DEVD-FMK on the functionality of platelets were analyzed by assessing their ability to bind to von Willebrand factor (vWF) and to aggregate in the presence of arachidonic acid and ristocetin. Cell survival was surveyed by MTT assay. RESULTS: At day 4 of storage, ristocetin-induced platelet aggregation was significantly higher in the inhibitor-treated (test) than in control samples; the difference was not significant at day 7. There was no significant difference in arachidonic acid-induced platelet aggregation between test and control samples. However, at day 7 of storage, the binding of platelets to vWF was significantly higher in test than in control samples. The MTT assay revealed significantly higher viability in test than in control samples at both days of study. CONCLUSION: Treatment of platelets with caspase-3 inhibitor could increase their functionality and survival.