A Moexitecan Magnetic Liposomal Strategy for Ferroptosis-Enhanced Chemotherapy

Abstract

Moexitecan (Mex) is a novel camptothecin derivative that retains the potent antitumor properties of camptothecin drugs and has improved hydrophilicity to enhance biocompatibility in vitro. However, single-drug therapy still has limitations. In this study, magnetic liposomes loaded with both moexitecan and superparamagnetic iron oxide nanoparticles (SPIO) have been fabricated by a film hydration and filtration method, which is abbreviated as Mex@MLipo. By using liposomes as drug carriers, Mex can be delivered specifically to the target site, resulting in improved therapeutic efficacy and reduced toxicity. Morphology characterization results show that Mex@MLipo has a mean diameter of 180–200 nm with a round morphology. The loading efficiencies of Mex and SPIO are 65.86% and 76.86%, respectively. Cell toxicity, in vitro cell uptake, and in vivo fluorescence imaging experiments showed that Mex@MLipo was the most effective in killing HT-29 cells compared with HepG-2 and PC-3 cells, due to its ability to combine chemotherapy and induce ferroptosis, resulting in a strong anti-tumor effect. Thus, this study developed an innovative nanoscale drug delivery system that paves the way for clinical applications of moexitecan.

Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements

“…Strengths and Limitations of Passive Targeting. Beyond the prototypical examples discussed, various nanoencapsulation techniques have emerged for CPT delivery, including nanoliposomes, 132 polymeric nanoparticles, 133 gold nanoparticles, 134 graphene oxide, 135 quantum dots, 136 and DNA nanostructures. 137 These ingenious systems effectively improve the solubility, stability, and pharmacokinetics of CPTs while mitigating toxic side effects.…”

Camptothecin-loaded supramolecular nanodelivery system based on amphiphilic calix[4]arene for targeted tumor therapy

“…Advances in recent research have demonstrated that liposomes and cyclodextrins can be used for the delivery of CPT to reduce its toxicity and promote its properties. 15–23 However, most of these carriers do not meet the requirements of a high drug-delivery efficiency, ease of dispersion, and controlled particle size, which are key to clinical translation. 24,25…”