Xiao-Jun Cai,Hai-Qing Dong,Wen-Juan Xia,Hui-Yun Wen,Xue-Quan Li,Jin-Hai Yu,Yong-Yong Li,Dong-Lu Shi
Engineered PEG-detachable catiomers were developed as non-viral gene vectors to detach the PEG layers responsive to the intracellular reducing environment. These catiomers were found to exhibit high DNA binding ability and reduced cytotoxicity, as evidenced in agarose gel electrophoresis and MTT assays. The size of the mPEG-SS-PLL/DNA complexes was around 100 nm with a regular spherical shape, as observed under transmission electron microscopy (TEM). The complexes were stably dispersed in an aqueous medium with 10% serum. However, fast aggregation was observed in the presence of 10 mM glutathione (GSH) due to detachment of the PEG segment via disulfide cleavage. These complexes showed high transfection efficiency in 293T and Hela cells under optimized conditions. The experimental results indicated that the mPEG-SS-PLL catiomers may have promising potential as a non-viral gene vector.
Hexiang Sun,Zachary Magnuson,Wenwen He,Weijie Zhang,Harsh Vardhan,Xiaolong Han,Gaohong He,Shengqian Ma
The desulfurization property of conventional mixed matrix membranes (MMMs) cannot meet the necessary demand due to particles aggregation and interface defects. Here, we put forward a layer-by-layer (LBL) approach to make a novel PEG@ZIF-8/poly(vinylidene difluoride)(PVDF) composite membrane for pervaporation desulfurization. In this way, a ZIF-8 layer is covered on the surface of the PVDF porous membrane via an in situ growth method. Then, a PEG layer is covered on the ZIF-8 layer by a casting method. Compared with pristine PEG membranes, the separation performance of the ZIF-8@PEG/PVDF nanocomposite membrane increased significantly. This can be attributed to the homogeneous ZIF-8 particle layer and better compatibility between the poly(ethylene glycol) (PEG) matrix and ZIF-8 particles. The membrane achieves a maximum total flux of 3.08 kg·m–2·h–1 at the third in situ growth cycles of ZIF-8 particles and a maximum sulfur enrichment factor of 7.6 at the sixth in situ growth cycles of ZIF-8 particles.
Through eliciting direct oncolysis, oncolytic viruses (OVs) induce release of tumor proteins, some of which can act as antigens to evoke an antitumor adaptive immune response. However, the poor immunogenicity and utilization efficiency of soluble tumor antigens limit the strength of the activated adaptive immune response and the clinical outcome of OVs. In this study, we found intratumoral injection of oncolytic virus, some of which was drained to the peritumoral lymph nodes. we proposed a strategy to modify oncolytic viruses (OVs) with antigen catchers (polyethylene glycol-linked maleimide) which efficiently capture tumor-derived proteins produced by oncolysis without diminishing its bioactivity of infecting tumor cells, then furtherly triggering enhanced antitumor adaptive immune response. In addition, the surface PEG layer protected AD 11 -Mal from the pre-exiting anti-AD 11 immunity to expand the applicability of AD 11 -Mal. Finally, we combined AD 11 -Mal with an indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl-tryptophan (1-MT) to overcome the local negative feedback in tumor immune microenvironment , which combinational regimen induced the long-lasting immune memory to inhibit tumor recurrence. In summary, our strategy greatly enhances the tumor antigen-specific adaptive immunity induced by OV therapy even in the presence of pre-exiting anti-OV immunity, which maybe promising for the development of next-generation OVs.
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