Supramolecular vehicles based on cyclodextrin for dual-function delivery of podophyllotoxin: Effective treatment for...

One promising approach to address the challenge of delivering anticancer medications to tumor tissues while minimizing harmful effects on healthy tissues is the use of self-assembling drug delivery systems (DDS). In this study, bifunctional cyclodextrins were designed using β-cyclodextrin as basic scaffold and incorporating sulfonamide groups for targeting. Cyclodextrin derivatives recognize podophyllotoxin and self-assemble into nanoparticles. The inclusion mode was determined through NMR, Job plot, and phase solubility curve analyses. XRD, FT-IR, and SEM further characterized its structural properties. DLS, TEM, and CAC experiments indicated that the inclusion complexes could self-assemble into nanoparticles with a size around 200 nm in aqueous solutions. The nanoparticles exhibited high stability as evidenced by zeta potential and Ks calculations. In vitro release experiments demonstrated that the nanoparticles readily dissociated and released their contents in acidic environments. In vitro inhibition assays, cytotoxicity assays, and uptake experiments further validated its excellent targeting ability, targeting cancer cells while retaining the potent drug toxicity of podophyllotoxin. Hemolysis tests confirmed its good biocompatibility. This study introduces a pH-responsive, targeting bifunctional drug delivery system for efficient tumor therapy, highlighting its promising potential for effective and targeted treatment.