scholarly journals A Gadolinium DO3A Amide m-Phenyl Boronic Acid MRI Probe for Targeted Imaging of Sialated Solid Tumors

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1459
Author(s):  
Christu Rajan ◽  
Jaya Seema ◽  
Yu-Wen Chen ◽  
Tsai-Chen Chen ◽  
Ming-Huang Lin ◽  
...  
Keyword(s):  
Boronic Acid ◽  
Time Window ◽  
Tumor Diagnosis ◽  
Targeted Imaging ◽  
Phenyl Boronic Acid ◽  
Cellular Labeling ◽  
Tumor Accumulation ◽  
Tumor Types

We developed a new probe, Gd-DO3A-Am-PBA, for imaging tumors. Our results showed active targeting of Gd-DO3A-Am-PBA to sialic acid (SA) moieties, with increased cellular labeling in vitro and enhanced tumor accumulation and retention in vivo, compared to the commercial Gadovist. The effectiveness of our newly synthesized probe lies in its adequate retention phase, which is expected to provide a suitable time window for tumor diagnosis and a faster renal clearance, which will reduce toxicity risks when translated to clinics. Hence, this study can be extended to other tumor types that express SA on their surface. Targeting and MR imaging of any type of tumors can also be achieved by conjugating the newly synthesized contrast agent with specific antibodies. This study thus opens new avenues for drug delivery and tumor diagnosis via imaging.

scholarly journals MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yipengchen Yin ◽  
Yongjing Li ◽  
Sheng Wang ◽  
Ziliang Dong ◽  
Chao Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Membranes ◽  
Imaging System ◽  
Fluorescence Signal ◽  
Bimodal Imaging ◽  
Red Blood Cell Membranes ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor Accumulation

Abstract Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

scholarly journals Selective Targeting of Breast Cancer by Tafuramycin a Using SMA-Nanoassemblies

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3532
Author(s):  
Ibrahim M. El-Deeb ◽  
Valeria Pittala ◽  
Diab Eltayeb ◽  
Khaled Greish
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptors ◽  
In Vivo Studies ◽  
Chemotherapy Agent ◽  
Anticancer Effects ◽  
Tumor Tissues ◽  
Potential Strategy ◽  
Tumor Accumulation

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of tumors that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. The mainstay of treatment remains chemotherapy, but the therapeutic outcome remains inadequate. This paper investigates the potential of a duocarmycin derivative, tafuramycin A (TFA), as a new and more effective chemotherapy agent in TNBC treatment. To this extent, we optimized the chemical synthesis of TFA, and we encapsulated TFA in a micellar system to reduce side effects and increase tumor accumulation. In vitro and in vivo studies suggest that both TFA and SMA–TFA possess high anticancer effects in TNBC models. Finally, the encapsulation of TFA offered a preferential avenue to tumor accumulation by increasing its concentration at the tumor tissues by around four times in comparison with the free drug. Overall, the results provide a new potential strategy useful for TNBC treatment.

scholarly journals NDUFA4L2 promotes glioblastoma progression, is associated with poor survival, and can be effectively targeted by apatinib

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Zheng Chen ◽  
Xiangyu Wei ◽  
Xueyi Wang ◽  
Xuan Zheng ◽  
Bowen Chang ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Hypoxia Inducible Factor ◽  
Mitochondrial Respiratory Chain ◽  
Metabolic Reprogramming ◽  
Tumor Cell Apoptosis ◽  
Survival Gene ◽  
A Subunit ◽  
Tumor Types

AbstractNADH dehydrogenase [ubiquinone] 1 alpha subcomplex, 4-like 2 (NDUFA4L2) is a subunit of Complex I of the mitochondrial respiratory chain, which is important in metabolic reprogramming and oxidative stress in multiple cancers. However, the biological role and molecular regulation of NDUFA4L2 in glioblastoma (GBM) are poorly understood. Here, we found that NDUFA4L2 was significantly upregulated in GBM; the elevated levels were correlated with reduced patient survival. Gene knockdown of NDUFA4L2 inhibited tumor cell proliferation and enhanced apoptosis, while tumor cells initiated protective mitophagy in vitro and in vivo. We used lentivirus to reduce expression levels of NDUFA4L2 protein in GBM cells exposed to mitophagy blockers, which led to a significant enhancement of tumor cell apoptosis in vitro and inhibited the development of xenografted tumors in vivo. In contrast to other tumor types, NDUFA4L2 expression in GBM may not be directly regulated by hypoxia-inducible factor (HIF)-1α, because HIF-1α inhibitors failed to inhibit NDUFA4L2 in GBM. Apatinib was able to effectively target NDUFA4L2 in GBM, presenting an alternative to the use of lentiviruses, which currently cannot be used in humans. Taken together, our data suggest the use of NDUFA4L2 as a potential therapeutic target in GBM and demonstrate a practical treatment approach.

scholarly journals Multifunctional Cyanine-Based Theranostic Probe for Cancer Imaging and Therapy

2021 ◽  
Vol 22 (22) ◽  
pp. 12214
Author(s):  
Cheng-Liang Peng ◽  
Ying-Hsia Shih ◽  
Ping-Fang Chiang ◽  
Chun-Tang Chen ◽  
Ming-Cheng Chang
Keyword(s):  
Photothermal Therapy ◽  
Radionuclide Therapy ◽  
Nuclear Imaging ◽  
Biological Evaluation ◽  
Targeted Radionuclide Therapy ◽  
Nir Fluorescence ◽  
Tumor Accumulation ◽  
Selective Accumulation

Cancer is one of the leading causes of death in the world. A cancer-targeted multifunctional probe labeled with the radionuclide has been developed to provide multi-modalities for NIR fluorescence and nuclear imaging (PET, SPECT), for photothermal therapy (PTT), and targeted radionuclide therapy of cancer. In this study, synthesis, characterization, in vitro, and in vivo biological evaluation of the cyanine-based probe (DOTA-NIR790) were demonstrated. The use of cyanine dyes for the selective accumulation of cancer cells were used to achieve the characteristics of tumor markers. Therefore, all kinds of organ tumors can be targeted for diagnosis and treatment. The DOTA-NIR790 labeled with lutetium-111 could detect original or metastatic tumors by using SPECT imaging and quantify tumor accumulation. The β-emission of 177Lu-DOTA-NIR790 can be used for targeted radionuclide therapy of tumors. The DOTA-NIR790 enabled imaging by NIR fluorescence and by nuclear imaging (SPECT) to monitor in real-time the tumor accumulation and the situation of cancer therapy, and to guide the surgery or the photothermal therapy of the tumor. The radionuclide-labeled heptamethine cyanine based probe (DOTA-NIR790) offers multifunctional modalities for imaging and therapies of cancer.

scholarly journals Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging

2022 ◽  
Vol 12 ◽  
Author(s):  
Leanne De Silva ◽  
Ju-Yen Fu ◽  
Thet Thet Htar ◽  
Wan Hamirul Bahrin Wan Kamal ◽  
Azahari Kasbollah ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Gamma Scintigraphy ◽  
Biodistribution Study ◽  
Scintigraphic Imaging ◽  
Tumor Bearing ◽  
Tumor Accumulation ◽  
Tumor Area

The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.

scholarly journals Guiding T lymphopoiesis from pluripotent stem cells by defined transcription factors

2019 ◽  
Author(s):  
Rongqun Guo ◽  
Fangxiao Hu ◽  
Qitong Weng ◽  
Cui Lv ◽  
Hongling Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Time Window ◽  
Immune Surveillance ◽  
Cell Stage ◽  
Immunodeficient Mice ◽  
Cell Transcriptome ◽  
T Lymphopoiesis

ABSTRACTAchievement of immunocompetent and therapeutic T lymphopoiesis from pluripotent stem cells is a central aim in T cell regenerative medicine. To date, preferentially regenerating T lymphopoiesis in vivo from pluripotent stem cells (PSC) remains a practical challenge. Here we documented that synergistic and transient expression of Runx1 and Hoxa9 restricted in the time window of endothelial to hematopoietic transition and hematopoietic maturation stages induced in vitro from PSC (iR9-PSC) preferentially generated engraftable hematopoietic progenitors capable of homing to thymus and developing into mature T (iT) cells in primary and secondary immunodeficient recipients. Single-cell transcriptome and functional analyses illustrated the cellular trajectory of T lineage induction from PSC, unveiling the T-lineage specification determined at as early as hemogenic endothelial cell stage and identifying the bona fide pre-thymic progenitors. The iT cells distributed normally in central and peripheral lymphoid organs and exhibited abundant TCRαβ repertoire. The regenerative T lymphopoiesis rescued the immune-surveillance ability in immunodeficient mice. Furthermore, gene-edited iR9-PSC produced tumor-specific-T cells in vivo that effectively eradicated tumor cells. This study provides insight into universal generation of functional and therapeutic T lymphopoiesis from the unlimited and editable PSC source.

scholarly journals SNAIL Promotes Metastatic Behavior of Rhabdomyosarcoma by Increasing EZRIN and AKT Expression and Regulating MicroRNA Networks

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1870 ◽  
Author(s):  
Klaudia Skrzypek ◽  
Marta Kot ◽  
Paweł Konieczny ◽  
Artur Nieszporek ◽  
Anna Kusienicka ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Cytoskeleton Reorganization ◽  
Cell Metastasis ◽  
Metastatic Behavior ◽  
Microrna Networks ◽  
Metastatic Involvement ◽  
Tumor Types ◽  
First Time

Rhabdomyosarcoma (RMS) is a predominant soft tissue tumor in children and adolescents. For high-grade RMS with metastatic involvement, the 3-year overall survival rate is only 25 to 30%. Thus, understanding the regulatory mechanisms involved in promoting the metastasis of RMS is important. Here, we demonstrate for the first time that the SNAIL transcription factor regulates the metastatic behavior of RMS both in vitro and in vivo. SNAIL upregulates the protein expression of EZRIN and AKT, known to promote metastatic behavior, by direct interaction with their promoters. Our data suggest that SNAIL promotes RMS cell motility, invasion and chemotaxis towards the prometastatic factors: HGF and SDF-1 by regulating RHO, AKT and GSK3β activity. In addition, miRNA transcriptome analysis revealed that SNAIL-miRNA axis regulates processes associated with actin cytoskeleton reorganization. Our data show a novel role of SNAIL in regulating RMS cell metastasis that may also be important in other mesenchymal tumor types and clearly suggests SNAIL as a promising new target for future RMS therapies.

Correlation between GC-C expression and uptake of GC-C-targeted imaging agents in vitro and in vivo

2010 ◽  
Vol 37 (6) ◽  
pp. 710
Author(s):  
Dijie Liu ◽  
Leonard R. Forte ◽  
Michael F. Giblin
Keyword(s):  
Imaging Agents ◽  
Targeted Imaging

scholarly journals Dominant-negative ATF5 rapidly depletes survivin in tumor cells

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Xiaotian Sun ◽  
James M. Angelastro ◽  
David Merino ◽  
Qing Zhou ◽  
Markus D. Siegelin ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Dominant Negative ◽  
Tumor Cell Death ◽  
Cell Penetrating ◽  
Selective Death ◽  
Tumor Types

Abstract Survivin (BIRC5, product of the BIRC5 gene) is highly expressed in many tumor types and has been widely identified as a potential target for cancer therapy. However, effective anti-survivin drugs remain to be developed. Here we report that both vector-delivered and cell-penetrating dominant-negative (dn) forms of the transcription factor ATF5 that promote selective death of cancer cells in vitro and in vivo cause survivin depletion in tumor cell lines of varying origins. dn-ATF5 decreases levels of both survivin mRNA and protein. The depletion of survivin protein appears to be driven at least in part by enhanced proteasomal turnover and depletion of the deubiquitinase USP9X. Survivin loss is rapid and precedes the onset of cell death triggered by dn-ATF5. Although survivin downregulation is sufficient to drive tumor cell death, survivin over-expression does not rescue cancer cells from dn-ATF5-promoted apoptosis. This indicates that dn-ATF5 kills malignant cells by multiple mechanisms that include, but are not limited to, survivin depletion. Cell-penetrating forms of dn-ATF5 are currently being developed for potential therapeutic use and the present findings suggest that they may pose an advantage over treatments that target only survivin.

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