Hollow Manganese-Based Nanoplatform for NIR-II/MRI Imaging-Guided Chemo/Chemodynamic/Photo-Therapy of Cancer

Abstract

Hollow manganese-dioxide-based nanoplatforms, which combine hollow structures with the intrinsic theranostic properties of Mn2+, have shown great potential for precise tumor diagnosis and treatment. However, single imaging or therapeutic modalities are still insufficient for high requirements of precise cancer theranostics. Herein, a hollow manganese-based theranostic nanoplatform, MnO2–IR-820-Q/DOX@TMTP1 nanocomposite (Mn-NCs), was designed and synthesized. With the assistance of the Mn-NCs, near-infrared-II (NIR-II, 900–1700 nm) fluorescence imaging with high spatial resolution and low autofluorescence was combined with magnetic resonance imaging (MRI) for highly efficient and precise multimodal imaging of cervical tumors. The organic cyanine dye IR-820 and PbS@CdS quantum dots (QDs) were integrated to form a hybrid nanocomposite (IR-820-Q) with strong NIR-II fluorescence emission, which was subsequently assembled onto a MnO2 nanocarrier to enable MRI and protect IR-820-Q from degradation. The hollow MnO2 nanoshells served as a nanoscale structural framework for IR-820-Q/DOX loading, tumor microenvironment-responsive degradation, and Mn2+-mediated imaging/therapeutic functions. The cervical tumor-targeting peptide TMTP1 was introduced to improve the tumor-targeting potential of the nanocomposite, enabling NIR-II fluorescence visualization of primary tumors and lymph node metastatic lesions. Therefore, Mn-NCs are well suited for tumor-targeted imaging-guided intervention of cervical cancer and lymphatic metastasis. By constructing the theranostic nanoplatform, the photothermal therapy (PTT) as well as photodynamic therapy (PDT) effect from the IR-820 was enhanced, and with the hydroxyl radicals (via Fenton-like reaction) of Mn2+ in the tumor microenvironment, effective chemodynamic therapy (CDT) was also achieved. The loading of doxorubicin (DOX) further endowed the nanoplatform with a chemotherapeutic capability. Thus, the developed theranostic nanoplatform showed strong NIR-II fluorescence/MRI-guided synergistic PTT/PDT/CDT and chemotherapy, which significantly improved the therapeutic outcomes. This study demonstrates a promising strategy for precise cervical cancer diagnosis and treatment, highlighting the potential of organic–inorganic hybrid nanomaterials for clinical translation.