Cu-based MOFs decorated dendritic mesoporous silica as tumor microenvironment responsive nanoreactor for enhanced tumor multimodal therapy

Nowadays, the therapeutic efficiency of tumor can be significantly influenced by the limitation of endogenous tumor microenvironment (TME). An ideal solution for improving therapeutic efficiency is constructing TME-responsive and multifunctional nanoreactor. Herein, a TME-responsive nanoreactor has been constructed using novel dendritic mesoporous silica nanoparticles (DMSNs) as the cornerstone, followed by anchoring platinum-(IV) prodrugs, loading photosensitizer indocyanine green (ICG), and decorating Cu2+ carboxylate MOFs. The prepared nanoreactor provides a high loading efficiency for Pt prodrugs and ICG, while the externally decorated MOFs can prevent premature leakage in neutral physiological environment at the same time. However, after accumulation at the tumor site, the outer MOFs can be rapidly decomposed in the TME to release Cu2+, which achieves efficient chemodynamic therapy (CDT) through Cu2+-triggered Fenton-like reaction and GSH depletion ability. At the same time, the released Pt drugs can achieve efficient chemotherapy. Moreover, the near-infrared (NIR) can activate the photodynamic and photothermal therapy (PDT&PTT) ability of ICG, resulting in PTT-enhanced CDT. Meanwhile, the nanoreactor can exhibit photothermal and magnetic resonance imaging (MRI) ability for highly specific diagnosis of tumor. Overall, this study provides a paradigm of TME-responsive nanoreactor for collaboratively multimodal enhanced tumor therapy.