PH-responsive supramolecular nanoparticles constructed by Cationic Pillar[5]arenes were used for drug delivery to enhance antitumor activity

Abstract

ABSTRACT Nano-drug delivery systems have been widely used in antitumor therapy due to their good biocompatibility and low toxicity. However, improving drug-carrying properties and drug release from carriers remains a challenge. In this study, we successfully constructed pH-responsive supramolecular drug-carrying spherical nanoparticles by self-assembling D-alanine-modified water-soluble cationic pillar[5]arene (DAP5) and sodium laurate (SL) to form complexes in aqueous solution. The results demonstrated that DAP5 spherical nanoparticles loaded with doxorubicin hydrochloride (DOX HCl) exhibited an encapsulation rate of 60.0% and a drug loading capacity of 10.5%. These nanoparticles continuously released the drug in a weakly acidic environment that simulates tumour cells. Furthermore, SL⊂DAP5 exhibited good biocompatibility with human normal liver cells (L-02) (IC50 >10 μmol/L), while DOX⊂SL⊂DAP5 demonstrated stronger cytotoxicity against four tumour cells (Hela, HepG2, MGC-803, T-24) compared to free DOX. Notably, DOX⊂SL⊂DAP5 showed an IC50 of only 1.04 μM for HepG2 cells, which was approximately 30.32% of that of DOX (3.43 μM) after 24 hours of incubation. These findings provide valuable insights for the future development of supramolecular drug delivery systems, aiming to enhance drug utilisation and reduce toxic side effects in tumour treatment.