Tumor-Specific Activatable Nanocarriers with Gas-Generation and Signal Amplification Capabilities for Tumor Theranostics.

Abstract

Multifunctional nanotheranostics are typically designed by integrating multiple functional components. This approach not only complicates the preparation process but also hinders any bioapplication due to the potential toxic effects when each component is metabolized. Here, we report a safe, biodegradable, and tumor-specific nanocarrier that, once activated by the acidic tumor microenvironment (TME), has diagnostic and therapeutic functions suitable for tumor theranostics. Our nanocarrier is composed of biomineralized manganese carbonate (BMC) nanoparticles (NPs) that readily decompose to release Mn²⁺ ions and CO₂ gas in the acidic TME due to its intrinsic pH-dependent solubility. Mn²⁺ and CO₂ release permits magnetic resonance and ultrasound imaging of tumors, respectively. These NPs can be loaded with the anticancer drug doxorubicin (DOX): BMC-DOX has high tumor inhibition effects both <i>in vitro</i> and <i>in vivo</i> due to combined Mn²⁺-mediated chemodynamic therapy and DOX-induced chemotherapy. This tumor-specific actuating nanocarrier might be a promising candidate for clinical translation.