RH-35

HEV-C1^VLP and Rat HEV Complete the Entry Step and Migrate into Human Target Cells.

Classically, HEV variants causing human infection belong to HEV-A. However, the increasing cases of rat HEV infection in humans since 2018 challenged this notion. Guo's team investigated the cell binding tropism of rat HEV and compared it with other HEV species using virus-like particles (HEV^VLPs)and infectious particles. They elucidated the mechanisms of zoonotic transmission and cross-protection among different HEV species.

Upon specific binding to the receptor(s), virions need to penetrate the cell membrane and enter the target cells to complete the so-called virus entry process. Herein, they inoculated HepG2 and RH-35 cells with the same amounts of VLPs. Consistent with their binding tropism, they detected marginal signal of HEV-C2^VLP within HepG2 and RH-35 cells, and no HEV-B^VLP and HEV-D^VLP signals (Fig. 1A-C). Nevertheless, significant amounts of HEV-C1^VLP and HEV-A^VLP were observed within HepG2 and RH-35 cells (Fig. 1A-C, column 1 and 3). Furthermore, in parallel with the entry of human HEV-3 in HepG2 cells, rat HEV entered HepG2 and RH-35 cells. More convincingly, both RT-qPCR and immunofluorescent analysis indicated that the entry of rat HEV into HepG2 and RH-35 cells was significantly inhibited by anti-HEV-C1^VLP serum (Fig. 1D-I). Collectively, these results demonstrated that HEV-C1^VLP and infectious rat HEV particles possess the capability to enter human target cells.

Tumor Targeted Assay of an Autologous Erythrocyte-Anchoring Strategy with a Closed-System Drug-Transfer Device

Chemotherapeutic agents are known to exhibit limited capacity for efficient localization to tumor sites when they are administered intravenously. This leads to off-target effects and poor accumulation in the desired target regions. Feng's team therefore designed an autologous ER-anchoring delivery strategy to potentiate the effects of chemotherapy drugs and mitigate adverse effects. A closed-system drug-transfer device was constructed for autologous ER procurement and immunogenicity attenuation. Doxorubicin (DOX) and indocyanine green (ICG) were encapsulated in autologous ERs and subsequently modified with DSPE-PEG-FA. The resulting DOX-ICG@ER-D was reinfused into circulation for the purpose of chemotherapy potentiation. In order to confirm that DOX-ICG@ER-D was capable of selectively accumulating within tumor cells, a coculture experiment was performed (Fig. 2A). At 24 h post-culture, they observed scant fluorescent DOX-ICG@ER-D localized to normal liver cells and bright fluorescence from liver tumor cells (RH-35) (Fig. 2B). Taken together, these data indicated that DOX-ICG@ER-D had a tumor-targeting capacity.