Multi-Armed Anti-CD40-Mediated Dual Drug Delivery System Based on Mesoporous Silica/Au Nanorod Nanocomposites for Multimodality Imaging and Combination Therapy

Nanotechnology provides the platform to develop functional nanocomposites with outstanding features, such as persistent luminescence (PL), photothermal conversion, magnetic resonance (MR), and so on, that has been incorporated in nanomedicine for diagnosis and therapy. Herein, the nanocomposites of ZnGa2O4:Cr3+ embedded in mesoporous silica coating surrounding gold nanorods (cGNR@MSNs) were developed for the codelivery of chemotherapeutic drugs and anti-CD40 antibodies. The nanocomposites were functionalized with tetrazaheterocycle linking divinylpyrimidine derivatives (DOTVs), which covalently capture anti-CD40 by disulfide re-bridging on the surface of cGNR@MSNs. The anti-CD40-mediated dual drug delivery system simultaneously realized the combination of chemo-, immuno-, and photothermal therapies, enhancing the synergistic effect of combination therapy for multiple tumor cells. Moreover, the nanodrug delivery system achieved multimodality imaging with fluorescence, PL, and MR modes for precise diagnosis. This study provides fascinating insights into the development of nanocomposite-based multimodality imaging strategies and imaging-guided combination therapies.