Wu, Y. et. al., Small Methods, 2026, e00760, 10, 1, https://doi.org/10.1002/smtd.202500760
Combined chemotherapy (CT) and gene therapy (GT) represent a reliable modality toward drug-resistant tumor treatment. Herein, a supramolecular polymeric scaffold is reported to co-load chemodrug paclitaxel (PTX) and Bcl-2 small interfering RNA (siRNA), respectively via hydrogen-bonding (H-bonding) association and electrostatic interaction, toward efficiently reversing drug resistance and significantly inhibiting tumor growth in a synergistic manner via GT-enhanced CT. The cationic shell consisting of P(OEGA-co-DMAEA) (poly(oligo(ethylene glycol) monomethyl ether acrylate-co-2-dimethylaminoethyl acrylate)) from resulting PTX-loaded micelles can steadily bind the negative siRNA via electrostatic interaction, finally to afford the targeted supramolecular micelleplexes PTX@PODHT/siRNA. The so generated nanoplatform possesses the enhanced co-loading capacity and transportation stability of PTX and siRNA and can induce pH-responsive cargos release within the tumor zone to effectively inhibiting tumor growth via synergistic CT/GT. © 2025 Wiley-VCH GmbH