In vitro analysis shows doxorubicin and combined therapies reverse multidrug resistance in HepG-2 cells, suggesting potential for effective cancer treatment.
To address chemotherapy limitations including systemic toxicity and multidrug resistance (MDR), we engineered degradable supramolecular polymer nanoparticles (Gla‐H6⊃D‐SS‐Fc NPs) based on supramolecular monomer (Gla‐H6⊃D‐SS‐Fc). This supramolecular monomer was constructed through host–guest interactions between galactose‐functionalized pillar[6]arene (Gla‐H6, host) and dopamine‐derived ferrocene‐cystamine (D‐SS‐Fc, guest), followed by oxidative self‐polymerization of dopamine groups to form stable nanoparticles (∼130 nm). The supramolecular polymer nanoparticles exhibited high doxorubicin (DOX) loading efficiency (50.5%) and pH/GSH‐triggered release kinetics. In vitro studies confirmed receptor‐mediated cellular uptake in HepG‐2 cells, enhanced tumor specificity, and low cytotoxicity toward normal hepatocytes (HL7702). Co‐delivery of DOX and siRNA synergistically suppressed P‐glycoprotein expression, reversing MDR in HepG‐2‐ADR cells. This supramolecular monomer‐based degradable polymer platform integrates tumor targeting, GSH/pH dual‐responsiveness, and combinatorial therapy, demonstrating significant clinical potential against chemoresistant tumors.
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Lu et al. (2025) studied this question.
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