Detachable\nCyclic\nPoly(ethylene glycol)-Embedded Choline\nPhosphate Liposome Used for Long-Acting and Accurate Cancer Chemo-Immunotherapy\nwith High Security

Liposomes have attracted attention\nin biomedicine and\npharmacy\nfor their benefits including reduced toxicity, extended pharmacokinetics,\nand biocompatibility. However, their limitations include susceptibility\nto blood clearance, rapid disintegration, and lack of functionality,\nrestricting their further applications. To address these challenges,\ninspired by the unique topological features of cyclic polymers and\nthe specific binding property of the choline phosphate (CP) lipid,\ndipole–dipole interactions between CP molecules are utilized\nto create a detachable cyclic PEG-embedded CP liposome (d-cycPEG-lipo).\nIn comparison to linear PEG-embedded liposomes (d-linPEG-lipo) and\nPEGylated liposomes (linPEG-lipo), d-cycPEG-lipo demonstrates enhanced\nresistance to proteins and macrophages in the bloodstream due to its\nhigher compactness and smoother interface. The packing behavior and\nlubrication property of cyclic PEG also result in reduced accumulation\nin organs, leading to an extended pharmacokinetic half-life of 13.6\nh. At the tumor site, the PEG embedded in d-cycPEG-lipo detached and\nfacilitated a 3.3-fold higher cell uptake than linPEG-lipo. Notably,\nd-cycPEG-lipo induces lower inflammation and triggers a stronger immune\nresponse than d-linPEG-lipo. In the treatment of breast cancer, d-cycPEG-lipo\nexhibits a significantly high efficacy of 98.5%. Hence, the reversible\ncombination of cyclic PEG with CP liposomes holds tremendous promise\nfor enhancing drug and antibody delivery in clinical tumor therapy.