Diketopyrrolopyrrole-based fluorescent probes for detection and bioimaging: Current progresses and perspectives

Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction. It is confirmed that the intracellular aggregation of TPSi NPs can highly amplify the acoustic scattering of the labeled MSCs, resulting in a 2.3-fold increase in the ultrasound (US) signal compared with that of unlabeled MSCs. The translational potential of the designed nanoagent for real-time US imaging-guided stem cell transplantation is confirmed via intramyocardial injection of labeled MSCs in a nude mouse model. It is proposed that the intracellular aggregation of protein drug-loaded TPSi NPs could be a simple but robust strategy for improving the therapeutic effect of stem cell therapy.

/pdf/cellular-internalization-induced-aggregation-of-porous-4s9t9ajqkn.pdf

Cellular Internalization-Induced Aggregation of Porous Silicon Nanoparticles for Ultrasound Imaging and Protein-Mediated Protection of Stem Cells

A facile synthesis of novel near-infrared pyrrolopyrrole aza-BODIPY luminogens with aggregation-enhanced emission characteristics.

Bone marrow-derived mesenchymal stem cells (BMSCs) have shown great potential for bone repair due to their strong proliferation ability and osteogenic capacity. To evaluate and improve the stem cell-based therapy, long-term tracking of stem cell differentiation into bone-forming osteoblasts is required. However, conventional fluorescent trackers such as fluorescent proteins, quantum dots, and fluorophores with aggregation-caused quenching (ACQ) characteristics have intrinsic limitations of possible interference with stem cell differentiation, heavy metal cytotoxicity, and self-quenching at a high labeling intensity. Herein, we developed aggregation-induced emission nanoparticles decorated with the Tat peptide (AIE-Tat NPs) for long-term tracking of the osteogenic differentiation of mouse BMSCs without interference of cell viability and differentiation ability. Compared with the ability of the commercial Qtracker 655 for tracking of only 6 passages of mouse BMSCs, AIE-Tat NPs have shown a much superior performance in long-term tracking for over 12 passages. Moreover, long-term tracking of the osteogenic differentiation process of mouse BMSCs was successfully conducted on the biocompatible hydroxyapatite scaffold, which is widely used in bone tissue engineering. Thus, AIE-Tat NPs have promising applications in tracking stem cell fate for bone repair.

Long-Term Tracking of the Osteogenic Differentiation of Mouse BMSCs by Aggregation-Induced Emission Nanoparticles.

Inflammatory breast cancer (IBC) is rare, but it is the most aggressive subtype of breast cancer. IBC has a unique presentation of diffuse tumor cell clusters called tumor emboli in the dermis of the chest wall that block lymph vessels causing a painful, erythematous, and edematous breast. Lack of effective therapeutic treatments has caused mortality rates of this cancer to reach 20%-30% in case of women with stage III-IV disease. Plasmonic nanoparticles, via photothermal ablation, are emerging as lead candidates in next-generation cancer treatment for site-specific cell death. Plasmonic gold nanostars (GNS) have an extremely large two-photon luminescence cross-section that allows real-time imaging through multiphoton microscopy, as well as superior photothermal conversion efficiency with highly concentrated heating due to its tip-enhanced plasmonic effect. To effectively study the use of GNS as a clinically plausible treatment of IBC, accurate three-dimensional (3D) preclinical models are needed. Here, we demonstrate a unique in vitro preclinical model that mimics the tumor emboli structures assumed by IBC in vivo using IBC cell lines SUM149 and SUM190. Furthermore, we demonstrate that GNS are endocytosed into multiple cancer cell lines irrespective of receptor status or drug resistance and that these nanoparticles penetrate the tumor embolic core in 3D culture, allowing effective photothermal ablation of the IBC tumor emboli. These results not only provide an avenue for optimizing the diagnostic and therapeutic application of GNS in the treatment of IBC but also support the continuous development of 3D in vitro models for investigating the efficacy of photothermal therapy as well as to further evaluate photothermal therapy in an IBC in vivo model.

https://www.dovepress.com/getfile.php?fileID=38123

Photothermal ablation of inflammatory breast cancer tumor emboli using plasmonic gold nanostars.

Mesenchymal stem cells (MSCs) have proved to be a promising and abundant cell source for tissue and organ repair in regenerative medicine. However, the cell fate, distribution and migration of these transplanted cells are still unclear due to the limited tracking methods. It is desirable to develop a biocompatible and photostable probe to label the MSCs for long-term tracking without affecting the cell proliferation and potency. Herein we apply a recently developed nanoprobe system, in which di(thiophene-2-yl)-diketopyrrolopyrrole (DPP) is covalently linked in the middle of polycaprolactone (PCL) forming the PCL-DPP-PCL polymer complex. Although the PCL-DPP-PCL nanoparticles uptaken by the MSCs did not affect the cell viability, it was interesting that they exhibited different effects on the multilineage potency of the MSCs in the subsequent differentiation in vitro. Specifically, we found that the PCL-DPP-PCL labeling was unfavorable to the MSC osteogenic differentiation, whereas the labeled MSCs exhibited the same adipogenic and chondrogenic differentiations compared to the unlabeled controls as verified by gene expressions and histological staining. Furthermore, the PCL-DPP-PCL nanoparticles remained strong fluorescence intensity even after 4 weeks of differentiation. This study indicated that PCL-DPP-PCL nanoparticles could be used for long-term cell tracing in MSC differentiation into adipogenic and chondrogenic lineages.

/pdf/long-term-tracking-mesenchymal-stem-cell-differentiation-1bvzvfrcpj.pdf

Long-Term Tracking Mesenchymal Stem Cell Differentiation with Photostable Fluorescent Nanoparticles

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Long-Term Tracking Mesenchymal Stem Cell Differentiation with Photostable Fluorescent Nanoparticles