Construction of Active-Passive Dual-Targeted Drug-Loaded Micelle Nanoparticles with Modified Dopamine Molecules for Efficient Anti-Tumor Therapy

Purpose This study designed a dopamine derivative integrating active targeting and pH-responsive borate ester bond-mediated passive targeting to construct drug delivery systems for tumor-targeted drug delivery, thus improving antitumor drug bioavailability and expanding the application of dopamine in drug delivery.Methods Nuclear magnetic resonance and Fourier transform infrared spectrometry were used to determine the structures of Man-PBA-DAO and Man-2PBA-DAO. Hydrodynamic diameter measurements confirmed the pH responsiveness of the targeting nanoparticles in different pH media over 12 hours. Nanoparticle toxicity was assessed using the MTT assay. Cellular uptake of the targeting nanoparticles was evaluated using flow cytometry and fluorescence microscopy. High-performance liquid chromatography (HPLC) was employed to quantify curcumin content.Results Covalent binding of mannose molecules to the dopamine derivative molecule allowed it to specifically target A549 cells with mannose receptors. More importantly, a significantly accelerated drug release (about 62% at pH=5.0) at low pH values was achieved by regulating the number of acidic-responsive borate bonds in polymer main chains. As a result, due to active targeting of mannose and passive targeting of acid response, Curcumin-loaded nanoparticles offer remarkably enhanced inhibiting efficiency against A549 cells at a low concentration of 6.25 μg/mL.Conclusion The dopamine derivative Man-2PBA-DAO-constructed dual active-passive targeting nano micelles enabled precise delivery and controllable release of Cur, offering new prospects for dopamine-based drug delivery in lung cancer treatment.