This study presents a novel approach in nanomedicine for targeted cancer therapy by leveraging folic acid-receptor (FR) interactions and reactive oxygen species (ROS)-responsive nanocarriers. Utilizing big data to advance nanomedicine, we developed an innovative amphiphilic conjugate, folic acid (FA) decorated dextran-block-poly copolymer (FA-Dex-b-PPS), designed to serve as ROS-responsive nanocarriers specifically for prostate cancer treatment. The chemical structure of FA-Dex-b-PPS was confirmed via Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. The self-assembly into ROS-responsive nanoparticles and subsequent degradation were characterized through fluorescence spectroscopy, dynamic light scattering, and transmission electron microscopy. Therapeutic nanocarriers encapsulating doxorubicin (Dox) were prepared via dialysis, demonstrating efficient oxidant-triggered Dox release in vitro. Cytotoxicity assays revealed high biocompatibility, with cell survival rates exceeding 85% at 400 μg/mL. Confocal laser scanning microscopy confirmed the efficient internalization of FA-Dex-b-PPS-Dox nanoparticles by PC3 cells via FR-mediated endocytosis, surpassing non-targeted Dex-b-PPS-Dox nanoparticles. Furthermore, in vitro and in vivo xenograft mouse model analyses consistently demonstrated that FA-Dex-b-PPS-Dox nanoparticles exhibited superior anti-tumor efficacy against PC3 cells compared to non-targeted and free Dox counterparts. These findings underscore the potential of tumor-targeted, ROS-responsive nanocarriers in enhancing the efficacy of cancer therapy.