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

Abstract

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.

Optically responsive delivery platforms: from the design considerations to biomedical applications

“…The cytokine release in the tumour stroma and the interaction of MSCs with cytokine and chemokine receptors present on the cell surfaces are mainly responsible for their migration towards tumours [238,239]. Xu et al [240] developed a synergistic treatment platform based on MSCs loaded with light-responsive plasmonic-magnetic hybrid NPs containing lipids, DOX, Au nanorods, and Fe 3 O 4 nanocluster (MSCs-LDGI) for photoacoustic imaging, targeted PTT, and chemotherapy against triple-negative breast cancer. Mesenchymal stem cells-LDGI maintained good bioactivity to migrate towards cancer cells both in vitro and in vivo.…”

“…The disassembly of the developed nanostructures with the subsequence drug release was probed upon light irradiation. In vitro and in vivo experiments showed that the MSCs-LDGI efficiently inhibited cancer cell growth and implemented good therapeutic effects via both local and intravenous injection routes [240]. In recent work, Muslimov et al [241] developed the light-sensitive MSCsbased delivery system.…”

“…However, despite all the advantages of light-responsive bioinspired delivery platforms, large size of cells can be a significant physical barrier that prevents complete dispersion of these cells in small vessels of the vascular network. This fact limits access of exogenously introduced cells to many target sites, including tumour tissues [236,240]. Despite the advantages of discussed bacteria-based drug systems, there are several challenges in their development and utilisation.…”

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

“…Mesenchymal stem cells have the highest enhanced migration and penetration abilities in tumours. It also showed the best antitumour efficacy in chemophotothermal therapy compared to other treatment groups in triple-negative breast cancer [ 201 ]. Another study showed a new strategy to use gold nanorod conjugated with polyacrylic acid/calcium phosphate (AuNR@PAA/CaP) yolk-shell NPs for dual-mode x-ray CT/PAI and PTT.…”

Intra-articular tracking of adipose-derived stem cells by chitosan-conjugated iron oxide nanoparticles in a rat osteoarthritis model

“…Osteoarthritis (OA) is the most common degenerative joint disease and still far from cure. Stem cell therapy is widely applied in tissue regeneration, 1,2 cancer treatment 3,4 and wound healing. 5 This stimulates researchers to restore diseased articular cartilage in OA patients via stem cell therapy.…”