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 MSCs-Engineered Biomimetic PMAA Nanomedicines for Multiple Bioimaging-Guided and Photothermal-Enhanced Radiotherapy of NSCLC

2021 ◽  
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.

73 APPLICATION OF QUANTUM DOT CONJUGATES FOR INVESTIGATING MAMMALIAN SPERMATOZOA

2012 ◽  
Vol 24 (1) ◽  
pp. 149
Author(s):  
J. M. Feugang ◽  
R. C. Youngblood ◽  
A. Fahad ◽  
J. M. Greene ◽  
S. T. Willard ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Imaging System ◽  
Renilla Luciferase ◽  
Control Group ◽  
Computer Assisted ◽  
Fluorescence Signal ◽  
Microscopic Evaluation ◽  
Mammalian Spermatozoa

Self-illuminating quantum dots are nanoparticles that are less than 100 nm in diameter. Their coating with the light-emitting protein Renilla luciferase forms complexes that have promising applications in in vivo imaging. These complexes can be further combined to specific tags such as antibodies or peptides for various in vitro studies. Especially in reproduction, these conjugates may contribute to a better comprehension of molecular events associated with fertilization and beyond. To this end, we evaluated the ability of mammalian spermatozoa to harmlessly incorporate nanoparticles. Motile spermatozoa of freshly collected boar and stallion semen were purified, washed in PBS/polyvinylpyrrolidone (PVP) (1 mg mL–1) and adjusted at desired concentrations according to experiments. Spermatozoa were fixed at 107 in Experiment 1 and incubated for 30 min at 37°C with 0, 1, or 5 nM quantum dots conjugated with the bioluminescence resonance energy transfer and R9 cell internalization peptide (BRET-Qdot-R9). In Experiment 2, different amounts of spermatozoa (25 × 106, 50 × 106 and 100 × 106) were incubated as in Experiment 1 with 0 or 1 nM BRET-Qdot-R9. After incubation, aliquots of BRET-Qdot-R9-loaded spermatozoa in both experiments were set aside for motility analysis using the computer-assisted sperm analyzer (only boar data shown). Remaining spermatozoa were centrifuged to eliminate the excess of BRET-Qdot-R9 and washed twice with PBS/PVP at 22°C. Resulting pellets were re-suspended with 50 μL of PBS/PVP and aliquots were mounted on slides for confocal fluorescence microscopic evaluation. Remaining cells and supernatants were mixed with 2 μg of coelenterazine and immediately imaged for bioluminescence using the IVIS-100 Imaging System. Experiments were repeated 3 times and analysed (Student's t-test; P < 0.05 for threshold of significance). Higher light emissions were detected in tubes containing both spermatozoa and BRET-Qdot-R9 as compared to the control (0 nM BRET-Qdot-R9) and last wash-derived supernatants. Low background signals of coelenterazine were observed in tubes (± sperm) without BRET-Qdot-R9. Experiment 1 revealed a dose-dependent response of BRET-Qdot-R9, whereas experiment 2 indicated a potential decrease of light emission with the higher sperm quantity. Interestingly, the presence of BRET-Qdot-R9 did not compromise sperm motility; however, the sperm/BRET-Qdot-R9 ratio appears essential to maintain comparable proportions of motile and rapid spermatozoa to the control group (86 ± 6 and 74 ± 5% for control vs 63 ± 17 and 46 ± 15%, 81 ± 8 and 68 ± 11% and 93 ± 1 and 85 ± 1% for 25 × 106, 50 × 106 and 100 × 106 sperm/1 nM ratios, respectively; P ≥ 0.05; mean ± standard error of the means). The BRET-Qdot-R9 fluorescence signal was mostly detected in the sperm head and intermediate piece with 1 nM BRET-Qdot-R9, whereas the entire spermatozoa fluoresced with 5 nM BRET-Qdot-R9. This study indicates that the incorporation of BRET-Qdot-R9 by boar and stallion spermatozoa does not impair their motility. Further investigations are needed to evaluate the proportion of cells incorporating BRET-Qdot-R9. Supported by the USDA-ARS Biophotonics Initiative #58-6402-3-0120.

Facile Preparation of Paclitaxel Nano-Suspensions to Treat Lung Cancer

2022 ◽  
Vol 12 (4) ◽  
pp. 690-694
Author(s):  
Wei Zhang ◽  
Yi Chen ◽  
Bin Wang ◽  
Xueren Feng ◽  
Lijuan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Loading ◽  
A549 Cells ◽  
Pharmaceutical Formulations ◽  
First Line ◽  
Facile Preparation ◽  
Tumor Accumulation ◽  
Line Chemotherapy

Lung cancer is a worldwide issue which account for the death of thousands every year. Paclitaxel (PTX) as the first line chemotherapy drug to treat lung cancer, its clinical applications is largely limited by its poor solubility. The facile preparation of pharmaceutical formulations to increase the solubility as well as targetability of PTX is of vital importance in lung cancer treatment. Herein, we introduced a facile method to prepare PTX nano-suspensions (NSs), which have high drug loading as well as well-dispersed particle size. The in vitro cell experiments revealed its capability to enhance the drug accumulation in A549 cells than free PTX. Moreover, in vivo animal assay suggested its better tumor accumulation and antitumor efficacy than PTX injection (Taxol).

Targeted Photodynamic Therapy (PDT) of Lung Cancer with Biotinylated Silicon (IV) Phthalocyanine.

2020 ◽  
Vol 21 ◽  
Author(s):  
Wenyi Dong ◽  
Ke Li ◽  
Shijie Wang ◽  
Ling Qiu ◽  
Qingzhu Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Imaging System ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
In Vitro Assays ◽  
Cancer Therapies ◽  
Lung Cancers

Background: Lung cancer is the leading cause of cancer-associated mortality in the world. Traditional cancer therapies prolong life expectancy of patients but often suffer from adverse reactions. Photodynamic therapy (PDT) has been recommended as a treatment option for lung cancer in several countries, due to its non-invasive procedures, high selectivity and weak side effects. Objective: We have designed and synthesized a biotin receptor-targeted silicon phthalocyanine (IV) (compound 1) which showed good therapeutic effect on biotin receptor-positive tumors. Since the overexpression of biotin receptor (BR) is also present in human lung cancer cells (A549), we explored the therapeutic properties of compound 1 on A549 xenograft tumor models. Method: The selectivity of compound 1 toward A549 cells was studied with fluorescence microscope and IVIS Spectrum Imaging System. The cytotoxicity was measured using MTT assay. In vivo anti-tumor activity was investigated on the nude mice bearing A549 xenografts. Results: In vitro assays proved that compound 1 could selectively accumulate in A549 cells via the BR-mediated internalization. In vivo imaging and distribution experiments showed that compound 1 could selectively accumulate in tumor tissues of tumor-bearing mice. After 16 days of the treatment, the volumes of tumor in PDT group were obviously smaller than that in other groups. Conclusion: This study demonstrates that compound 1 is a promising photosensitizer and has broad application prospects in clinical PDT of lung cancers.

Multi-mode light microscopy of microtubule assembly dynamics and chromosome movement in vivo and In vitro

1996 ◽  
Vol 54 ◽  
pp. 730-731
Author(s):  
E. D. Salmon ◽  
J. C. Waters ◽  
C. Waterman-Storer
Keyword(s):  
Imaging System ◽  
Ccd Camera ◽  
Transmitted Light ◽  
Microtubule Assembly ◽  
Live Cells ◽  
Optical Efficiency ◽  
Multiple Band ◽  
Multi Mode

We have developed a multi-mode digital imaging system which acquires images with a cooled CCD camera (Figure 1). A multiple band pass dichromatic mirror and robotically controlled filter wheels provide wavelength selection for epi-fluorescence. Shutters select illumination either by epi-fluorescence or by transmitted light for phase contrast or DIC. Many of our experiments involve investigations of spindle assembly dynamics and chromosome movements in live cells or unfixed reconstituted preparations in vitro in which photodamage and phototoxicity are major concerns. As a consequence, a major factor in the design was optical efficiency: achieving the highest image quality with the least number of illumination photons. This principle applies to both epi-fluorescence and transmitted light imaging modes. In living cells and extracts, microtubules are visualized using X-rhodamine labeled tubulin. Photoactivation of C2CF-fluorescein labeled tubulin is used to locally mark microtubules in studies of microtubule dynamics and translocation. Chromosomes are labeled with DAPI or Hoechst DNA intercalating dyes.

scholarly journals USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription

2021 ◽  
Author(s):  
Xiaohua Jie ◽  
William Pat Fong ◽  
Rui Zhou ◽  
Ye Zhao ◽  
Yingchao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Affinity Purification ◽  
Smad Signaling ◽  
Lung Cancer Patients ◽  
Lysine Specific Demethylase ◽  
Underlying Mechanisms ◽  
H3k9me3 Level ◽  
Critical Binding

AbstractRadioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

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.

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