比較聚丙烯胍和聚乙烯亞胺：與癌細胞膜的作用機制和癌細胞通透性變化

Abstract

胍基和胺基具有與細胞膜反應並進入細胞的能力，此特徵在癌症疾病治療上具有很高的效益與潛力。在研究中，帶有胍基的聚丙烯胍被合成，並將此材料與帶有胺基的聚乙烯亞胺進行比較，探討其與癌細胞膜的作用方式及對細胞通透性變化的影響。結論指出，聚乙烯亞胺能在細胞存率高的同時造成癌細胞膜的完好性破壞，使分子從細胞內漏到細胞外的通透性上升，聚丙烯胍則無顯示此現象。值得關注的是，聚乙烯亞胺造成的細胞膜受損並不會增加分子進入細胞的能力，顯示出只影響通細胞內到細胞外的單向通透性。除此之外，我們觀測到活癌細胞核膜能夠有效地阻擋聚丙烯胍和聚乙烯亞胺的進入，而固定後的細胞則沒有此效果。在結合能力實驗中，相比於聚乙烯亞胺，聚丙烯胍展現出更強的脫氧核醣核酸連結能力。最後，從細胞滲透性測試中，我們得知聚丙烯胍和聚乙烯亞胺對癌細胞單層的緊密連接有具大的破壞力，造成緊密連接的表現量降低並使細胞間隙運輸的顯著上升。 聚丙烯胍具有比聚乙烯亞胺強的脫氧核醣核酸連結能力，此特性未來在基因治療上能有很大的應用。另外，聚丙烯胍和聚乙烯亞胺都能破壞緊密連結的表現，未來能實驗設計能在癌細胞球上進行，測試此兩種材料在模擬的癌細胞環境中，能否同樣有降低緊密連結表現量的效果，並評估兩種材料在臨床的應用性。

Guanidine and amine groups possess the ability to interact with cell membranes and penetrate cells, demonstrating significant potential and benefits for cancer treatment. In this study, we synthesized poly(allylguanidine) (PAG) containing a guanidine group and compared it with polyethylenimine (PEI) containing an amine group to investigate their interaction mechanisms with cancer cell membranes and their effects on cellular permeability. The study revealed that PEI destroyed the integrity of the cancer cell membrane while maintaining high cell viability, resulting in an increase in molecule permeability from the inside to the outside of the cell, a phenomenon not observed with PAG. Notably, the membrane damage caused by PEI did not enhance the permeability of molecules entering the cells, indicating that it only affected unidirectional permeability from the intracellular to the extracellular space. Additionally, we observed that the nuclear membranes of live cancer cells effectively excluded the entry of both PAG and PEI, whereas fixed cells did not exhibit this effect. In binding ability experiments, PAG demonstrated stronger DNA binding ability compared to PEI. Finally, in cellular permeability tests, we found that both PAG and PEI had a disruptive effect on tight junctions of cancer cell monolayer, leading to a decrease in tight junction expression and a significant increase in paracellular transport. PAG had stronger DNA binding capabilities than PEI, which had significant applications in gene therapy in the future. Additionally, both PAG and PEI could disrupt the expression of tight junctions. Future experimental designs could involve testing these two materials on cancer cell spheroids to determine if they similarly reduce tight junction expression in a mimicking cancer cell environment. This would help evaluate the clinical applicability of both materials.