Facile Synthesis of Amino Alcohol‐Grafted Polydopamine Nanoparticles for Controlled Doxorubicin Release in Cancer Treatment

ABSTRACT Cancer continues to be a leading cause of mortality globally, and chemotherapy often faces challenges related to poor selectivity and significant systemic toxicity. In this study, we developed novel polydopamine nanoparticles (PDA‐NPs) functionalized with various amino alcohols, specifically alaninol, valinol, and leucinol, to evaluate their anticancer activity. The successful conjugation of amino alcohols with the functional groups of PDA was confirmed using Fourier transform infrared spectroscopy (FTIR), x‐ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and scanning electron microscopy with energy‐dispersive x‐ray spectroscopy (SEM‐EDX). The highest drug loading percentage was observed in valinol‐ and alaninol‐modified nanoparticles. Cumulative release studies demonstrated a pH‐dependent drug release profile, with enhanced release in acidic conditions characteristic of the tumor microenvironment. Additionally, MTT assay results indicated the biocompatibility of the NPs both before and after loading with doxorubicin (Dox), with Dox@PDA‐Al NPs and free Dox significantly reducing the viability of HCT‐116 cancer cells. confocal microscopy further demonstrated increased cellular uptake, mitochondrial membrane disruption, and elevated reactive oxygen species (ROS) production. Overall, amino alcohol‐functionalized PDA‐NPs present a pH‐sensitive and effective nanocarrier platform, showing considerable promise for safer and more efficient cancer chemotherapy.