Octreotide-modified pH-responsive nanocomposites for ultrasound imaging-guided chemo-photothermal therapy of prostate...

Prostate cancer remains a major malignancy in men, and its clinical management is still limited by insufficient tumor-specific imaging, inefficient drug delivery, and suboptimal therapeutic efficacy. Herein, we developed an octreotide-modified, pH-responsive polymer-mineral hybrid nanoplatform, IDOCP@CC, for ultrasound imaging-guided chemo-photothermal therapy of prostate cancer. The nanocomposites were constructed by loading doxorubicin and IR825 into octreotide-conjugated PF127-PAsp polymeric micelles, followed by in situ CaCO₃ mineralization. IDOCP@CC exhibited a spherical core-shell structure, an average hydrodynamic diameter of approximately 220 nm, positive surface charge, and high encapsulation efficiencies for doxorubicin and IR825 of 79.05% and 76.86%, respectively. Under weakly acidic conditions, IDOCP@CC promoted drug release and generated CO₂ bubbles from the CaCO₃ shell, resulting in enhanced B-mode and contrast-enhanced ultrasound signals. The nanocomposites also showed stable photothermal performance under 808 nm near-infrared irradiation and enhanced cellular uptake in PC3 cells. In vitro, IDOCP@CC combined with NIR irradiation markedly increased reactive oxygen species generation, induced apoptosis and cell death, inhibited migration and colony formation, and promoted immunogenic cell death-associated signals. In PC3 xenograft-bearing nude mice, IDOCP@CC accumulated efficiently in tumors, enhanced contrast-enhanced ultrasound imaging, elevated tumor temperature under NIR irradiation, achieved a tumor inhibition rate of 69%, reduced serum PSA levels, downregulated β-catenin expression, and showed no obvious systemic toxicity. These findings suggest that IDOCP@CC is a promising octreotide-modified and pH-responsive theranostic nanoplatform for ultrasound imaging-guided chemo-photothermal therapy of prostate cancer.