Redox-sensitive dimeric paclitaxel choline phosphate nanoliposomes for improved anticancer efficacy

Abstract

The use of paclitaxel (PTX) in clinical practice has been limited by its inadequate solubility in water. Although marketed PTX liposomes solve the problem of poor water solubility of PTX, their popularization has still been hindered by their low drug loading content and poor targeted release. Now, zwitterionic liposomes containing choline phosphate (CP) have been developed as a nanocarrier for anticancer therapy. These liposomes have a reversed charge orientation compared to conventional phosphorylcholine (PC) liposomes, and offer improved biocompatibility, bioorthogonality, and enhanced cellular uptake efficiency. Here, we study a redox-triggered PTX liposome (PTX-SS-CP) system based on PTX disulfide CP conjugates (PTX-SS-CP), which were synthesized by introducing PTX into CP by a disulfide bond linker. To verify the consistent size of PTX-SS-CPs, both dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques were employed, and they exhibited a uniform size of 130–180 nm and a very high drug loading content (>30 wt%). The PTX-SS-CPs were evaluated for their anticancer effects through in vitro and in vivo analyses. The results demonstrate that the PTX-SS-CPs exhibit rapid release, high cellular uptake capacity, and improved anticancer efficiency under reductive conditions (GSH), and the PTX-SS-11-CPs showed significantly stronger tumor targeting efficacy and growth inhibition compared to other PTX-SS-CP groups in in vivo studies. The PTX-SS-CP system, which is activated by redox reactions, exhibits a redox-sensitive PTX release mechanism that enhances its antitumor efficacy. This system has the potential to be used as a liposomal PTX delivery system for tumor therapy.