Jiahao Wang,Zhirong Chen,Peiyi Zhao,Yajia Wang,Jiang Chen,Quankui Lin
Up to 50% of individuals with uveal melanoma (UM), a frequent cancer of the eye, pass away from metastases. One of the major challenges in treating UM is the role of receptor tyrosine kinases (RTKs), which mediate the epithelial-mesenchymal transition (EMT) of tumors. RTKs are involved in binding multiple growth factors, leading to angiogenesis and vasculogenic mimicry (VM) phenomena. Currently, most anti-angiogenic drugs have shown a tendency to increase the VM of tumors in clinical trials, resulting in limited efficacy. The existing gap in UM treatment lies in the lack of effective strategies to target RTK-mediated EMT and VM. While some approaches have been attempted, there is still a need for novel therapeutic interventions that can specifically interfere with these processes. This research employed the gene vector PEI-g-PEG to interfere with the platelet derived growth factor-alpha receptor (PDGFR-α)-mediated EMT process, thereby retarding the growth of UM. The cell experiments demonstrated that the gene polyplex exhibited favorable cell uptake and lysosome escape properties, effectively suppressing the expression of PDGFR-α protein and EMT marker proteins and the occurrence of VM phenomenon. In vivo animal studies also inhibited the growth of UM, and PAS assays showed that the treatment reduced the generation of VM in tumor tissue. This study broadens the application of PEI-g-PEG while interfering with the RTK-mediated tumor EMT process with the help of RNAi technology, providing a new idea for tumor reduction research.
Chong Wang,Rong-Chao Xue,Ze-Zhong Lin,Xing-Ping Zhang,Pei-Yao Chen,Yu Chen,Hai-Chao Li
Flexible plasticized poly(vinyl chloride) (PPVC) is widely used in medical devices; however, achieving persistent antibiofouling functionality after significant mechanical deformation and long-term water exposure remains a critical challenge. In this work, we introduce amphiphilic heterografted multi-arm star copolymers, polyethylenimine (PEI) cores functionalized with polyethylene glycol (PEG) and poly(ε-caprolactone) (PCL) arms (denoted as PEI-g-PEG-PCLs), as multifunctional additives for modifying PPVC. Dynamic light scattering (DLS) and optical transmittance measurements confirmed the formation of PEI-g-PEG-PCL micelles within the PPVC matrix. The incorporation of PEI-g-PEG-PCLs improved not only the mechanical and thermal properties of PPVC but also its surface hydrophilicity. The resulting composites demonstrated exceptional resistance to biofouling, reducing protein adsorption by 96.2–97.3 % for bovine serum albumin and 98.0–99.8 % for lysozyme, and lowering bacterial adhesion rates to 11 % for Escherichia coli and 19 % for Staphylococcus aureus. Furthermore, platelet adhesion and hemolysis assays confirmed the biocompatibility of the PEI-g-PEG-PCL/PPVC composites. Notably, even after undergoing three cycles of 50 % strain, the optimal PEI-g-PEG-PCL/PPVC composite retained over 91 % of its initial anti-protein fouling performance. Long-term immersion in physiological conditions (28 days) further demonstrated its durability, with more than 92 % of the original antifouling efficacy maintained. The multi-arm star topology accompanied with the long PCL arm is proposed to resolve the “entanglement–migration paradox” commonly encountered in linear or less branched polymer additives. This study presents a molecular engineering strategy for developing durable antibiofouling polymers capable of withstanding both mechanical stress and prolonged aqueous exposure in medical applications.
危险品化学品经营许可证（带存储）