Anti-Tumor Metastasis via Platelet Inhibitor Combined with Photothermal Therapy under Activatable Fluorescence/Magnetic Resonance Bimodal Imaging Guidance
Xu Zhang, Xiaoda Li, Suhui Sun, Ping Wang, Xiaotu Ma, Rui Hou, Xiaolong Liang
Abstract
Photothermal therapy (PTT) is a promising tumor therapy strategy; however, heterogeneous heat distribution over the tumor often exists, resulting in insufficient photothermal ablation and potential risk of cancer metastasis, which has been demonstrated to be associate with platelets. Herein, a near-infrared (NIR) photothermal agent of IR780 was conjugated with MRI agent of Gd-DOTA via a disulfide linkage (ICD-Gd), which was coassembly with lipid connecting tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) (DSPE-PEG-CREKA) to encapsulate a platelet inhibitor of ticagrelor (Tic), affording a multistimuli-responsive nanosystem (DPC@ICD-Gd-Tic). The nanosystem with completely quenching fluorescence could specifically target the tumor-associated platelets and showed pH/reduction/NIR light-responsive drug release, which simultaneously resulting in dis-assembly of nanoparticle and fluorescence recovery, enabling the drug delivery visualization in tumor in situ via activatable NIR fluorescence/MR bimodal imaging. Finally, DPC@ICD-Gd-Tic further integrated the photoinduced hyperthermia and platelet function inhibitor to achieve synergistic anticancer therapy, leading to ablation of primary tumor cells and effectively suppressed their distant metastasis. The number of lung metastases in 4T1 tumor bearing mice was reduced by about 90%, and the size of tumor was reduced by about 70%, while half of the mouse was completely cured by this smart nanosystem.