The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.

/pdf/photothermal-therapy-and-photoacoustic-imaging-via-5cxqag870v.pdf

Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

Applications of Phosphorene and Black Phosphorus in Energy Conversion and Storage Devices

2D nanomaterials with unique nanosheet structures, large surface areas, and extraordinary physicochemical properties have attracted tremendous interest. In the area of nanomedicine, research on graphene and its derivatives for diverse biomedical applications began as early as 2008. Since then, many other types of 2D nanomaterials, including transition metal dichalcogenides, transition metal carbides, nitrides and carbonitrides, black phosphorus nanosheets, layered double hydroxides, and metal-organic framework nanosheets, have been explored in the area of nanomedicine over the past decade. In particular, a large surface area makes 2D nanomaterials highly efficient drug delivery nanoplatforms. The unique optical and/or X-ray attenuation properties of 2D nanomaterials can be harnessed for phototherapy or radiotherapy of cancer. Furthermore, by integrating 2D nanomaterials with other functional nanoparticles or utilizing their inherent physical properties, 2D nanomaterials may also be engineered as nanoprobes for multimodal imaging of tumors. 2D nanomaterials have shown substantial potential for cancer theranostics. Herein, the latest progress in the development of 2D nanomaterials for cancer theranostic applications is summarized. Current challenges and future perspectives of 2D nanomaterials applied in nanomedicine are also discussed.

2D Nanomaterials for Cancer Theranostic Applications

Titanium carbide MXene quantum dots (QDs) were synthesized using an effective fluorine-free method as a biocompatible and highly efficient nanoagent for photothermal therapy (PTT) applications. In contrast to the traditional, hazardous and time-consuming process of HF pretreatment, our fluorine-free method is safe and simple. More importantly, abundant Al oxoanions were found to be modified on the MXene QD surface by the fluorine-free method, which endowed the QDs with strong and broad absorption in the NIR region. As a result, the as-prepared MXene QDs exhibited an extinction coefficient as large as 52.8 Lg-1 cm-1 at 808 nm and a photothermal conversion efficiency as high as 52.2%. Both the values are among the best reported so far. The as-prepared MXene QDs achieved simultaneous photoacoustic (PA) imaging and the remarkable PTT effect of tumors. Moreover, MXene QDs showed great biocompatibility without causing noticeable toxicity in vitro and in vivo, indicating their high potential for clinical applications.

Fluorine-free preparation of titanium carbide MXene quantum dots with high near-infrared photothermal performances for cancer therapy.

Black phosphorus (BP), also known as phosphorene, has attracted recent scientific attention since its first successful exfoliation in 2014 owing to its unique structure and properties. In particular, its exceptional attributes, such as the excellent optical and mechanical properties, electrical conductivity and electron-transfer capacity, contribute to its increasing demand as an alternative to graphene-based materials in biomedical applications. Although the outlook of this material seems promising, its practical applications are still highly challenging. In this review article, we discuss the unique properties of BP, which make it a potential platform for biomedical applications compared to other 2D materials, including graphene, molybdenum disulphide (MoS2), tungsten diselenide (WSe2) and hexagonal boron nitride (h-BN). We then introduce various synthesis methods of BP and review its latest progress in biomedical applications, such as biosensing, drug delivery, photoacoustic imaging and cancer therapies (i.e., photothermal and photodynamic therapies). Lastly, the existing challenges and future perspective of BP in biomedical applications are briefly discussed.

Black phosphorus and its biomedical applications

Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal therapy.

As a new kind of two-dimensional (2D) material, black phosphorus (BP) has attracted explosive interest in biomedical applications. It is well-recognized that the biomedical performances of nanoparticles depend not only on their properties, but also on their structures and dimensions. Here in this study, we successfully prepared three kinds of BP nanosheets with different sizes, then systematically investigated their cytocompatibility and photothermal effects to ablate cancer cells. It is evident from various assays that all the three BP samples have excellent cytocompatibility, and the BP nanosheets with a large size have better photothermal efficiency for cancer cell ablation. Our findings may provide a new insight into the fundamental cyto-performances of BP.

/pdf/different-sized-black-phosphorus-nanosheets-with-good-uzddl0ev7y.pdf

Different-sized black phosphorus nanosheets with good cytocompatibility and high photothermal performance

Osteogenic differentiation and bone formation are tightly regulated by several factors, including microRNAs (miRNAs). However, miRNA expression patterns and function during mechanical loading-induced osteogenic differentiation of human periodontal ligament cells (PDLCs) remain unclear. Here, we investigated the differential expression of miRNA-195-5p in the periodontal tissues of mice under orthodontic mechanical loading and in primary human PDLCs exposed to a simulated tension strain. The miR-195-5p was observed to be down-regulated and negatively correlated with osteogenic differentiation. Overexpression of miR-195-5p significantly inhibited PDLC differentiation under cyclic tension strain (CTS), whereas the functional inhibition of miR-195-5p yielded an opposite effect. Further experiments confirmed that WNT family member 3A (WNT3A), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein receptor-1A (BMPR1A), proteins important for osteogenic activity and stability, were direct targets of miR-195-5p. Mechanical loading increased the WNT3A, FGF2, and BMPR1A protein levels, while miR-195-5p inhibited WNT3A, FGF2, and BMPR1A protein expression. WNT, FGF, and BMP signaling were involved in osteogenic differentiation of PDLCs under CTS. Further study confirmed that reintroduction of WNT3A and BMPR1A can rescue the inhibition of miR-195-5p on osteogenic differentiation of PDLCs. Our findings are the first to demonstrate that miR-195-5p is a mechanosensitive gene that plays an important role in mechanical loading-induced osteogenic differentiation and bone formation.

MicroRNA-195-5p Regulates Osteogenic Differentiation of Periodontal Ligament Cells Under Mechanical Loading.

Orthodontic tooth movement (OTM) is associated with bone remodeling mediated by orthodontic mechanical loading. Increasing studies reported that Wnt signaling played crucial roles in mechanical stimuli induced bone remodeling. However, little is known about the involvement of Wnt signaling in orthodontic force-induced bone formation during OTM. In virtue of the OTM mice model as we previously reported, where new bone formation was determined by micro-CT and immunoreactivity of osteocalcin and osterix, we explored the activation of Wnt signaling pathway during OTM. Our results proved the nuclei translocation of β-catenin, suggesting the activation of canonical Wnt signaling pathway in the periodontal ligament cells (PDLCs) near the alveolar bone at the tension site (TS). Moreover, the immunoreactivity of Wnt5a, but not Wnt3a in PDLCs indicated the activation of canonical Wnt pathway might be mediated by Wnt5a, but not Wnt3a as in most cases. The co-location of Wnt5a and β-catenin that was evidenced by double labeling immunofluorescence staining further supported the hypothesis. In addition, the high expression of FZD4 and LRP5 in PDLCs at TS of periodontium suggested that the activation of Wnt signaling pathway was mediated by these receptors. The negligible expression of ROR2 also indicated that canonical but not non-canonical Wnt signaling pathway was activated by Wnt5a, since previous studies demonstrated that the activation of canonical/non-canonical Wnt signaling pathway was largely dependent on the receptors. In summary, we here reported that Wnt5a mediated activation of canonical Wnt signaling pathway might contribute to the orthodontic force induced bone remodeling.

Wnt5a mediated canonical Wnt signaling pathway activation in orthodontic tooth movement: possible role in the tension force-induced bone formation

Periodontal remodeling and alveolar bone resorption and formation play essential roles during orthodontic tooth movement (OTM). In the process, human periodontal ligament cells (HPDLCs) sense and respond to orthodontic forces, contributing to the alveolar bone formation. However, the underlying mechanism in this process is not fully elucidated. In the present study, cyclic stress stimulus was applied on HPDLCs to mimic the orthodontic forces during OTM. Our results demonstrated that cyclic stretch promoted the osteogenic differentiation of HPDLCs. Moreover, our data suggested that yes-associated protein (YAP), the Hippo pathway effector, which also involved in mechanical signaling transduction, was activated as we found that the nuclear translocation of YAP was significantly increased in the cyclic stress treated HPDLCs. The mRNA expression of CTGF and CYR61, the target genes of YAP, was also remarkably increased. Furthermore, knockdown of YAP suppressed the cyclic stretch induced osteogenesis in HPDLCs, while overexpression of YAP in HPDLCs enhanced osteogenesis. We also noticed that YAP activities could be suppressed by the ROCK and nonmuscle myosin II inhibitors, Y-27632 and Blebbistatin. The inhibitors also significantly inhibited the cyclic stretch induced osteogenesis in HPDLCs. Finally, in the murine OTM model, our results revealed that YAP was upregulated and nuclearly translocated in the PDLCs at the tension side. In summary, our present study demonstrated that cytoskeleton remodeling induced activation of YAP signaling pathway was crucial for the cyclic stretch-induced osteogenesis of HPDLCs, which might play important roles during OTM.

/pdf/cyclic-stretch-enhances-osteogenic-differentiation-of-human-r4hie48l6q.pdf

Guangli Han

Papers

Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal therapy.

Different-sized black phosphorus nanosheets with good cytocompatibility and high photothermal performance

MicroRNA-195-5p Regulates Osteogenic Differentiation of Periodontal Ligament Cells Under Mechanical Loading.

Wnt5a mediated canonical Wnt signaling pathway activation in orthodontic tooth movement: possible role in the tension force-induced bone formation

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation.