Highly luminescent and photostable near-infrared fluorescent polymer dots for long-term tumor cell tracking in vivo

2016 ◽  
Vol 4 (2) ◽  
pp. 202-206 ◽  
Author(s):  
Liqin Xiong ◽  
Yixiao Guo ◽  
Yimin Zhang ◽  
Fengwen Cao

Near-infrared-emitting polymer dots were prepared and used as fluorescent nanoprobes for in vitro HeLa cell labeling and in vivo long-term HeLa tumor tracking. The prepared NIR polymer dots showed no obvious effect on the tumor growth, and exhibited durable brightness, long-term photostability and high sensitivity.

2016 ◽  
Vol 4 (48) ◽  
pp. 7845-7851 ◽  
Author(s):  
Junpeng Shi ◽  
Meng Sun ◽  
Xia Sun ◽  
Hongwu Zhang

Near-infrared persistent luminescence hollow mesoporous nanospheres have been synthesized via a template method. These nanospheres can be used as large capacity drug carriers and realize super long-term and high sensitivity tracking of drug delivery in deep tissue.


2013 ◽  
Vol 754 ◽  
pp. 21-87 ◽  
Author(s):  
Zeid A. Al Othman ◽  
Mohammad Mezbaul Alam ◽  
Mu. Naushad ◽  
Inamuddin ◽  
Mohd Farhan Khan

Nanomedicine is a relatively new field of science and technology. By interacting with biomolecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Current and potential applications of nanotechnology in medicine range from research involving diagnostic devices, drug delivery vehicles to enhanced gene therapy and tissue engineering procedures. Its advantage over conventional medicine lies on its size. Operating at nanoscale allows to exploit physical properties different from those observed at microscale such as the volume/surface ratio. This allows drugs of nanosize be used in lower concentration and has an earlier onset of therapeutic action. It also provides materials for controlled drug delivery by directing carriers to a specific location. Inorganic nanomedicine is likely to remain one of the most prolific fields of nanomedicine, which refers to the use of inorganic or hybrid (inorganic-inorganic or inorganic-organic) nanomaterials (INMs) and nanoparticles (INPs) to achieve innovative medical advances for body parts implantation, drug and gene discovery and delivery, discovery of biomarkers, and molecular diagnostics. Among the most promising INMs being developed are metal, silica, dendrimers, organic-inorganic hybrids, ceramics (e.g. ZrO2, TiO2, Al2O3, etc.) and bioinorganic hybrids. Metal NP contrast agents enhance magnetic resonance imaging and ultrasound results in biomedical applications of in vivo imaging. Hollow and porous INMs have been exploited for drug and gene delivery, diagnostic imaging, and photothermal therapy. Biomolecular inorganic nanohybrids and nanostructured biomaterials have been exploited for targeted imaging and therapy, drug and gene delivery, and regenerative medicine. Potential uses for fluorescent quantum dots (QDs) include cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. Biocompatible QD conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastasis cell tracking. This article outlines present developments and future prospects for the use of Ti-based NPs and NMs in experimental in vivo and in vitro studies and in engineering nanodevices and biosensors for clinical and investigative use in diagnosis and therapy in diverse fields of medical sciences, such as oncology, infection control, orthopedics, dentistry, dermatology, genetics, cardiology, ophthalmology, etc. Toxicological considerations of these INPs and INMs are also discussed.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
John Terrovitis ◽  
Keng Fai Kwok ◽  
Riikka Läutamaki ◽  
James M Engles ◽  
Andreas S Barth ◽  
...  

Background. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo . Aim. To develop a reporter gene that permits in vivo stem cell labeling. We examined the sodium-iodide symporter (NIS), a protein that is not expressed in the heart, but promotes cellular uptake of 99m Tc or 124 I, thus permitting cell tracking by SPECT or PET imaging, respectively. Methods. The human NIS gene ( h NIS) was expressed in rat cardiac derived stem cells (rCDCs) using lentivirus driven by the CAG or CMV promoter. NIS function in transduced cells was confirmed by in vitro 99m Tc uptake. Eleven rats were injected with 1 or 2 million rCDCs intramyocardially immediately after LAD ligation; 6 with CMV-NIS and 5 with CAG-NIS cells. Dual isotope SPECT imaging was performed on a small animal SPECT/CT system, using 99m Tc for cell detection and 201 Tl for myocardial delineation, 24 hrs after cell injection. PET was performed on a small animal PET scanner using 124 I for cell tracking and 13 NH 3 for myocardial delineation, 48hrs after cell injection. Contrast Ratio (CR) was defined as [(signal in the cells)-(signal in blood pool)]/signal in blood pool. High resolution ex vivo SPECT scans of explanted hearts (n=3) were obtained to confirm that in vivo signal was derived from the cell injection site. The presence of h NIS mRNA was confirmed in injected hearts after animal sacrifice (n=2), by real-time RT-PCR. Results. NIS expression in rCDCs did not affect cell viability/proliferation (p=0.718, ctr vs NIS). In vitro 99m Tc uptake was 6.0±0.9% vs 0.07±0.05, without and with perchlorate (specific NIS blocker), respectively. NIS-transduced rCDCs were easily visualized as spots of 99m Tc or 124 I uptake within a perfusion deficit in the SPECT and PET images. CR was considerably higher when cells were transduced by the CMV-NIS virus in comparison to the CAG-NIS virus (70±40% vs 28±29%, p=0.085). Ex vivo small animal SPECT imaging confirmed that in vivo 99m Tc signals were localized to the injection sites. PCR confirmed the presence of h NIS mRNA in injected hearts. Conclusion. NIS expression allows non invasive in vivo stem cell tracking in the myocardium, using both SPECT and PET. This reporter gene has great potential for translation in future clinical applications.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Na Xie ◽  
Ya Hou ◽  
Shaohui Wang ◽  
Xiaopeng Ai ◽  
Jinrong Bai ◽  
...  

Abstract Imaging in the second near-infrared II (NIR-II) window, a kind of biomedical imaging technology with characteristics of high sensitivity, high resolution, and real-time imaging, is commonly used in the diagnosis of brain diseases. Compared with the conventional visible light (400–750 nm) and NIR-I (750–900 nm) imaging, the NIR-II has a longer wavelength of 1000–1700 nm. Notably, the superiorities of NIR-II can minimize the light scattering and autofluorescence of biological tissue with the depth of brain tissue penetration up to 7.4 mm. Herein, we summarized the main principles of NIR-II in animal models of traumatic brain injury, cerebrovascular visualization, brain tumor, inflammation, and stroke. Simultaneously, we encapsulated the in vivo process of NIR-II probes and their in vivo and in vitro toxic effects. We further dissected its limitations and following optimization measures.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3778-3778
Author(s):  
Bartosch Wojcik ◽  
Fabian Lang ◽  
Susanne Badura ◽  
Anja Vogel ◽  
Tamara Tesanovic ◽  
...  

Abstract Introduction: Transforming events in B-lineage (ALL) occur primarily at the level of committed progenitor cells, but the phenotype, frequency and hierarchical organization of leukemia-initiating cells (LICs) are controversial. Pronounced clonal heterogeneity in ALL and the lack of preclinical models impede functional analysis of LICs and dissecting the clonal architecture of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Aims and methods: To identify cellular features associated with cell fate and decisions, engraftment potential, growth kinetics and resistance to therapy of BCP-ALL LICs at the clonal level, we generated multiple single-cell-derived clones from patient derived-long-term cultures (PD-LTCs) of human BCP-ALL. This in vitro ALL-LTC model allows prolonged serum-, cytokine-, and stroma-free culture of patient-derived BCP-ALL cells that are largely stable in terms of cytogenetic and immunophenotypic features for up to 6 months [Nijmeijer B et. al, Exp Hematol. 2009;37:376; Badura S et al., PLoS One. 2013; 8:e80070] Three ALL-LTCs were selected on the basis of different patterns of surface marker expression and cytogenetics, i.e. Ph+ ALL (LTCs PH and BV; common-ALL) and BCR-ABL negative ALL (LTC CR; pre B-ALL), respectively. Results: Clonogenic growth in semisolid medium ranged from 0.25% to 8% for these ALL-LTCs (CR 8%, PH 0.45% and BV 0.25%), consistent with functional diversity within the bulk as well as the immunophenotypically defined subsets. To analyze these subpopulations at the clonal level, we isolated leukemic cell subsets by cell sorting on the basis of CD20, CD34 and CD38 expression, and then generated hundreds of clones by expanding single-cell sorted subpopulations. All sorted cell fractions from all three ALL-LTCs were capable of initiating long-term growth in vitro. In limiting dilution cultures, 1% to 5% of single sorted cells derived from these cell fractions gave rise to prolonged leukemic cell growth. To evaluate the leukemia-initiating capacity of the clonal ALL subpopulations in vivo, we examined engraftment and outgrowth kinetics of different ALL clones in a xenograft model with sublethally irradiated NSG mice. Individual clones derived from different sorted subpopulations displayed pronounced differences in engraftment potential and aggressiveness based on analyses of blood, bone marrow and spleen. This ranged from rapid appearance of ALL and death within 70-80 days (clone PH 20), to complete lack of leukemic outgrowth 155 days after transplantation (clone PH clone 14). The other four clones derived from this ALL (PH) displayed intermediate engraftment and outgrowth kinetics. Notably, leukemogenic properties were not associated with a distinct surface marker profile based in CD20, CD34 and CD38 expression. A similar heterogeneity of leukemogenic potential was determined with clonal subpopulations from the LTC BV. To assess the hierarchical relationship between different clones and the association with LIC capacity, we examined the pattern of immunoglobulin VDJ-rearrangement of different clones. The Ig rearrangement patterns confirm that the clones represent distinct clonal populations derived from the original polyclonal LTC, but we observed no hierarchical relationship with respect to the biological properties of different clones. Further functional evaluation of these subclones was performed by videomicroscopy-based single cell tracking that allows analysis of individual cells and their progeny over many cell divisions. We observed concordance between cell cycle length and cell death events as determined by single cell tracking and the engraftment potential and aggressiveness of LTCs derived single cell clones in vivo. To elucidate the molecular basis for the biologic differences between the clonal ALL populations, we compared highly and poorly leukemogenic clones by SILAC based proteomics. Only 5% of 6500 proteins measured in clones differing in their leukemia-initiating potential were differentially regulated, and these proteins could be assigned to a limited number of pathways. In conclusion, comparative evaluation of clonal lymphoblast populations generated from patient-derived ALL long-term cultures by combined in vitro analysis, single cell videomicroscopy, xenotransplantation and proteomics is a promising approach to identify specific markers and therapeutic strategies that target LIC in ALL. Disclosures Wojcik: Novartis: Research Funding, Travel, Accommodation Other; SAnofi Aventis: Consultancy, Travel, Accommodation, Travel, Accommodation Other. Lang:Novartis: Research Funding, Travel, Accommodation Other. Brüggemann:Amgen Inc.: Consultancy, Research Funding.


Author(s):  
Paul Karl Horan ◽  
Meryle J. Melnicoff ◽  
Bruce D. Jensen ◽  
Sue E. Slezak

Blood ◽  
2010 ◽  
Vol 115 (26) ◽  
pp. 5347-5354 ◽  
Author(s):  
Francois Lassailly ◽  
Emmanuel Griessinger ◽  
Dominique Bonnet

Abstract Determining how normal and leukemic stem cells behave in vivo, in a dynamic and noninvasive way, remains a major challenge. Most optical tracking technologies rely on the use of fluorescent or bioluminescent reporter genes, which need to be stably expressed in the cells of interest. Because gene transfer in primary leukemia samples represents a major risk to impair their capability to engraft in a xenogenic context, we evaluated the possibility to use gene transfer–free labeling technologies. The lipophilic dye 3,3,3′,3′ tetramethylindotricarbocyanine iodide (DiR) was selected among 4 near-infrared (NIR) staining technologies. Unfortunately we report here a massive transfer of the dye occurring toward the neighbor cells both in vivo and in vitro. We further demonstrate that all lipophilic dyes tested in this study (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine perchlorate [DiI], DiD, DiR, and PKH26) can give rise to microenvironmental contamination, including when used in suboptimal concentration, after extensive washing procedures and in the absence of phagocytosis or marked cell death. This was observed from all cell types tested. Eventually, we show that this microenvironmental contamination is mediated by both direct cell-cell contacts and diffusible microparticles. We conclude that tracking of labeled cells using non–genetically encoded markers should always be accompanied by drastic cross validation using multimodality approaches.


2015 ◽  
Vol 26 (5) ◽  
pp. 817-821 ◽  
Author(s):  
Liqin Xiong ◽  
Fengwen Cao ◽  
Xinmin Cao ◽  
Yixiao Guo ◽  
Yimin Zhang ◽  
...  

2018 ◽  
Vol 6 (47) ◽  
pp. 7871-7876 ◽  
Author(s):  
Sitong Chen ◽  
Shuang Cui ◽  
Rongxin Du ◽  
Ming Liu ◽  
Wei-Kai Tsai ◽  
...  

Highly fluorescent conjugated polymer dots with aggregation-induced emission fluorogen were applied in in vitro and in vivo cell imaging.


2020 ◽  
Vol 172 ◽  
pp. 107837 ◽  
Author(s):  
Kaiping Wang ◽  
Gang Nie ◽  
Siqi Ran ◽  
Huiling Wang ◽  
Xiqiu Liu ◽  
...  

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