GSH-activatable DSM-cRGD nanoprobe enables NIR-II imaging-guided breast cancer surgery and enhances chemo/chemodynamic therapy
Background
Achieving precise tumor margin delineation during surgery and controlled drug release intratumorally remain significant challenges in breast cancer therapy. Current approaches often lead to incomplete resections or systemic side effects due to non-specific drug distribution. Tumor microenvironment (TME)-responsive nanoplatforms offer a promising solution by leveraging unique tumor biochemical properties, such as elevated glutathione (GSH) levels, to enable targeted imaging and treatment. This strategy aims to improve therapeutic efficacy and reduce off-target toxicity by activating only within the tumor.
Study Design
Researchers developed a glutathione (GSH)-activatable theranostic nanoprobe, DSM-cRGD, designed for second near-infrared (NIR-II) fluorescence imaging. This probe consists of Nd-doped rare-earth nanoparticles coated with a manganese dioxide (MnO2) shell and functionalized with a cyclic RGD peptide for specific αvβ3-integrin targeting. The MnO2 shell initially quenches NIR-II fluorescence, which is then activated upon GSH-responsive degradation within the TME. For therapeutic applications, doxorubicin (DOX) was loaded onto the nanoprobe, creating DSM-cRGD@DOX, to enable simultaneous release of DOX and Mn2+ ions for synergistic effects. The study evaluated its targetability, imaging capabilities, and therapeutic efficacy in a tumor model.
Results
The DSM-cRGD nanoprobe demonstrated GSH-responsive activation, with the MnO2 shell degrading within the TME to unquench NIR-II fluorescence. This enabled real-time, high-contrast surgical navigation, indicating strong targetability within tumors via specific binding to αvβ3-integrin. The therapeutic variant, DSM-cRGD@DOX, facilitated the simultaneous release of doxorubicin and Mn2+ ions upon MnO2 degradation. This dual release mechanism induced synergistic chemodynamic and chemotherapeutic effects. > The combined therapy further triggered immunogenic cell death, activating anti-tumor immune responses and effectively suppressing tumor recurrence and metastasis.
Key Findings
- DSM-cRGD nanoprobe provides GSH-activatable NIR-II fluorescence for high-contrast tumor imaging.
- Cyclic RGD peptide enables strong
αvβ3-integrintargeting within tumors for surgical navigation. - DSM-cRGD@DOX facilitates synergistic chemo/chemodynamic therapy via DOX and
Mn2+release. - The combined therapy induces immunogenic cell death, activating anti-tumor immune responses.
- The platform effectively suppresses tumor recurrence and metastasis in a tumor model.
Why It Matters
This integrated DSM-cRGD nanoplatform offers a significant advancement for precision breast cancer management, addressing critical limitations in both surgical accuracy and therapeutic efficacy. By providing real-time, high-contrast NIR-II imaging, surgeons could achieve more complete tumor resections, potentially reducing recurrence rates. Furthermore, the synergistic chemo/chemodynamic therapy, coupled with TME-responsive drug release, promises enhanced anti-tumor effects and activation of the body's own immune system. While currently preclinical, this approach lays groundwork for future clinical strategies that could minimize side effects and improve long-term outcomes for patients, representing a novel protocol for targeted drug delivery and surgical guidance.
breast cancer
nanomedicine
rgd
doxorubicin
nir-ii imaging
chemodynamic therapy