Multimodal Imaging-Guided Tumor Microenvironment-Responsive Nanoplatform for Synergistic Therapy of Pancreatic Cancer

Purpose: Chemotherapy remains an effective treatment for pancreatic cancer. However, the limitations of single-modal therapies and the absence of imaging-based monitoring during treatment pose challenges for real-time optimization of drug delivery, resulting in suboptimal therapeutic outcomes. Methods: This study aims to design and develop a novel nanoparticle drug delivery system, HMP-ICG&DOX, which incorporates indocyanine green (ICG) as an FDA-approved near-infrared photothermal agent and doxorubicin (DOX) as a commonly used chemotherapeutic drug. The modification with NH 2 -PEG-NH 2 enhances the biocompatibility of the nanocarrier. The designed nanoprobe exhibits the following features: (1) It decomposes in the tumor microenvironment (TME) to release Mn 2+ for magnetic resonance T 1 imaging, while ICG provides near-infrared fluorescence imaging capabilities. (2) It facilitates synergistic photothermal-chemotherapy, significantly improving therapeutic efficacy against pancreatic cancer. (3) The pH-responsive drug release enhances drug utilization efficiency while minimizing side effects. Results: Experimental results demonstrate that HMP-ICG&DOX nanoparticles possess excellent biocompatibility, antitumor activity, controlled drug release, and multimodal imaging tracking abilities. Conclusion: In conclusion, the HMP-ICG&DOX nanoparticles designed in this study offer promising applications in the diagnosis and treatment of pancreatic cancer.