A Light-Triggered Mesenchymal Stem Cell Delivery System for Photoacoustic Imaging and Chemo-Photothermal Therapy of Triple Negative Breast Cancer.

Targeted therapy is highly challenging and urgently needed for patients diagnosed with triple negative breast cancer (TNBC). Here, a synergistic treatment platform with plasmonic-magnetic hybrid nanoparticle (lipids, doxorubicin (DOX), gold nanorods, iron oxide nanocluster (LDGI))-loaded mesenchymal stem cells (MSCs) for photoacoustic imaging, targeted photothermal therapy, and chemotherapy for TNBC is developed. LDGI can be efficiently taken up into the stem cells with good biocompatibility to maintain the cellular functions. In addition, CXCR4 on the MSCs is upregulated by iron oxide nanoparticles in the LDGI. Importantly, the drug release and photothermal therapy can be simultaneously achieved upon light irradiation. The released drug can enter the cell nucleus and promote cell apoptosis. Interestingly, light irradiation can control the secretion of cellular microvehicles carrying LDGI for targeted treatment. A remarkable in vitro anticancer effect is observed in MDA-MB-231 with near-infrared laser irradiation. In vivo studies show that the MSCs-LDGI has the enhanced migration and penetration abilities in the tumor area via both intratumoral and intravenous injection approaches compared with LDGI. Subsequently, MSCs-LDGI shows the best antitumor efficacy via chemo-photothermal therapy compared to other treatment groups in the TNBC model of nude mice. Thus, MSCs-LDGI multifunctional system represents greatly synergistic potential for cancer treatment.