Multimodal Imaging-Guided Spatiotemporal Tracking of Photosensitive Stem Cells for Breast Cancer Treatment.

Stem cell therapy has shown great potential in treating a wide range of diseases including cancer. The real-time tracking of stem cells with high spatiotemporal resolution and stable imaging signals remains the bottleneck to evaluate and monitor therapeutic outcomes once transplanted into patients. Here, we developed a photosensitive mesenchymal stem cell (MSC) loaded with mesoporous silica-coated gold nanostars (MGNSs) integrated with indocyanine green for spatiotemporal tracking and imaging-guided photothermal therapy (PTT) in treating breast cancers. The MGNS served as a stable imaging probe with multifunctional properties for photoacoustic imaging (PAI), fluorescence imaging, and PT imaging. Owing to the excellent PT stability of MGNSs, long-term three-dimensional (3D) PAI was achieved to monitor stem cells in real time at the tumor site, while the tumor structure was imaged using 3D B-mode ultrasound imaging. PAI revealed that the photosensitive stem cells reached the widest distribution area at the tumor site post 24 h of intratumoral injection, which was further confirmed via two-dimensional (2D) PT and fluorescence imaging. With this optimal cell distribution window, in vivo studies showed that the photosensitive stem cells via both intratumoral and intravenous injections successfully inhibited breast cancer cell growth and decreased the tumor recurrence rate post PTT. Our results support that this photo-integrated platform with stable optical properties is promising to achieve real-time tracking and measure the cell distribution quantitatively with high spatiotemporal resolution for stem cell therapy.

Water extract of ginseng and astragalus regulates macrophage polarization and synergistically enhances DDP's anticancer effect.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, supplementing Qi and strengthening body resistance are an important principle of anticancer treatment. Panax ginseng C.A.Mey. (ginseng) and Astragalus membranaceus Bunge (astragalus) are the representative herbs for this therapeutic principle. AIM OF THE STUDY: This study aims to explore the effect of the water extract of ginseng and astragalus (WEGA) on regulating macrophage polarization and mediating anticancer in the tumor microenvironment. MATERIALS AND METHODS: A549 cells were cultured in tumor-associated macrophage (TAM) supernatant with various concentrations of WEGA (0, 5, 10, 20 mg/mL). A549 cell proliferation was determined through methyl thiazole tetrazolium (MTT) assay and real-time cell analysis (RTCA), respectively. In vivo experiments were performed with a Lewis lung cancer (LLC) xenograft mouse model. Forty-eight mice were divided into six groups and treated with saline, WEGA, or cis-diamine dichloro platinum (DDP) with dosage of WEGA (0, 30, 60, 120 mg/kg body weight/day). The different groups were administered with drugs via oral or intraperitoneal injection once a day for 21 consecutive days. Tumor inhibition rate, spleen index, thymus index, cytokine, protein, and mRNA expression levels were detected in mice. RESULTS: In a co-culture system, WEGA remarkably inhibited A549 cell proliferation, promoted the expression of M1 macrophage markers and inhibited M2 TAMs markers. Therefore, WEGA affected the biological behavior of cancer cells by regulating the expression of some markers relevant to macrophage polarization. In addition, the group of WEGA and DDP chemotherapy effectively inhibited the transplanted tumor growth in mice and improved weight loss and immunosuppressive with the cisplatin inducing. CONCLUSIONS: This study provides mechanistic insights into the anticancer effect of WEGA through the regulation of macrophage polarization and highlights that WEGA could be a novel option for integrative cancer therapies.

OCF can repress tumor metastasis by inhibiting epithelial-mesenchymal transition involved in PTEN/PI3K/AKT pathway in lung cancer cells.

A component formula with definite compositions provides a new approach to treat various diseases. Salvia miltiorrhiza and Panax ginseng are widely used in China because of their antitumor properties. In the previous study, the optimizing component formula (OCF), prepared with salvianolic acids, ginsenosides, and ginseng polysaccharides (5, 10, and 5 mg·L-1, respectively) extracted from S. miltiorrhiza and P. ginseng on the basis of IC50 in lung cancer A549 cells and damage minimization on human bronchial epithelial cells in vitro. Currently, we also have demonstrated the inhibitory effect of OCF on A549 cell migration and invasion in vitro. According to Lewis lung cancer cells (LLC) allograft in C57BL/6 mice and A549 xenograft in nude mice experiment, we found that the anti-tumor and anti-metastasis effects of OCF treatment were related to the inhibition of epithelial-mesenchymal transition (EMT). Further studies showed that the inhibitory effect of OCF on EMT was associated with the PTEN/PI3K/AKT pathway. Therefore, all studies revealed that OCF could prevent cancer progression and tumor metastasis by inhibiting EMT involved PTEN/PI3K/AKT signaling pathway in lung cancer cells.