scholarly journals pH-Sensitive and Long-Circulation Nanoparticles for Near-Infrared Fluorescence Imaging-Monitored and Chemo-Photothermal Synergistic Treatment Against Gastric Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yun Zhou ◽  
Xuanzi Sun ◽  
Liansuo Zhou ◽  
Xiaozhi Zhang
Keyword(s):  
Gastric Cancer ◽  
Near Infrared ◽  
Therapeutic Option ◽  
Drug Loading ◽  
Gastric Cancer Cell Line ◽  
Postoperative Treatment ◽  
Maximum Temperature ◽  
Hydrodynamic Diameter

Gastrectomy is the primary therapeutic option for gastric cancer. Postoperative treatment also plays a crucial role. The strategy to improve the postoperative prognosis of gastric cancer requires a combined system that includes a more efficient synergistic treatment and real-time monitoring after surgery. In this study, photothermal-chemotherapy combined nanoparticles (PCC NPs) were prepared via π-π stacking to perform chemo-photothermal synergistic therapy and continuous imaging of gastric cancer. PCC NPs had a spherical morphology and good monodispersity under aqueous conditions. The hydrodynamic diameter of PCC NPs was 59.4 ± 3.6 nm. PCC NPs possessed strong encapsulation ability, and the maximum drug loading rate was approximately 37%. The NPs exhibited extraordinary stability and pH-response release profiles. The NPs were rapidly heated under irradiation. The maximum temperature was close to 58°C. PCC NPs showed good biocompatibility both in vitro and in vivo. Moreover, the NPs could effectively be used for in vivo continuous monitoring of gastric cancer. After one injection, the fluorescent signal remained in tumor tissues for nearly a week. The inhibitory effect of PCC NPs was evaluated in a gastric cancer cell line and xenograft mouse model. Both in vitro and in vivo evaluations demonstrated that PCC NPs could be used for chemo-photothermal synergistic therapy. The suppression effect of PCC NPs was significantly better than that of single chemotherapy or photothermal treatment. This study lays the foundation for the development of novel postoperative treatments for gastric cancer.

scholarly journals Sequential Drug Delivery By Injectable Macroporous Hydrogels For Combined Photodynamic-Chemotherapy

2021 ◽  
Author(s):  
Yuanyuan Zhong ◽  
Li Zhang ◽  
Shian Sun ◽  
Zhenghao Zhou ◽  
Yunsu Ma ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Early Stage ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Sequential Release ◽  
Therapy Effect ◽  
Hollow Mesoporous Silica

Abstract With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.

CD44-overexpressed gastric cancer imaging by near IR using HA-based supramolecular hydrogels.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 34-34
Author(s):  
Jungmin Park
Keyword(s):  
Gastric Cancer ◽  
Optical Imaging ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Gastric Cancer Cell Line ◽  
Cancer Cell Line ◽  
Gastric Cancer Cells

34 Background: To establish NIR optical probe based on the HA-based supramolecular hydrogels (HASHs) conjugated with Cy5.5 for CD44-overexpressed gastric cancer imaging. Methods: To establish HASHs, Cy5.5 NHS ester was conjugated with polyethyleneimine (PEI, 25k Da) and mixed with hyaluronic acid (HA, 1M Da) by an electric interaction. The optimazed ideal molar ratio of PEI to HA was confirmed by DLS and gel electrophoresis. The CD44-expression level for various gastric cancer cell lInes (MKN1, MKN28, MKN45, MKN72, AGS, and N87 cells) was evaluated by FACS analysis. For establishment of the gastric cancer xenograft model, CD44-overexpressed gastric cancer cells were implanted into the BALB/c nude mouse's proximal thigh region. For in vitro targeting study, the cellular affinity of HASHs for CD44-low expressed gastric cancer cell line and CD44-overexpressed gastric cancer cell line was verified by confocal microscopy and IHC staing. For in vivo NIR imaging, HASHs were injected into established xenograft mouse via tail vein and NIR optical imaging was conducted time-dependently. Results: The colloidal size of HASHs was 1.4 micrometer and their morphology was confirmed by electron microscopy. CD44-expression level of MKN45 cells was 92.53% that was higher than MKN28 cells (2.66%). After the treatment of HASHs, the endocytosis into the cytosol was examined for MKN45 cells, but not observed in MKN28 cells due to the deficiency of CD44. 30 days after the transplantion of MKN45 cells, for in vivo imaging study, the prepared HASHs were intraveneously injected into tumor-bearing mouse model. By NIR optical imaging, the optical intensity at tumor site was enhanced upto 3 hours and the maximum intensity was 350 times larger than normal tissue. Conclusions: HASHs was established using supramolecular HA and Cy5.5-conjugated PEI for the targeted imaging of CD44-overexpressed gastric cancer cells. In vitro and in vivo studies demonstrated that SHAHs can visualize the individualized CD44-overexpressed gastric cancer cells by non-invasive optical imaging.

scholarly journals A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Hai Wang ◽  
Pranay Agarwal ◽  
Shuting Zhao ◽  
Jianhua Yu ◽  
Xiongbin Lu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Encapsulation Efficiency ◽  
Near Infrared ◽  
Drug Loading ◽  
Eukaryotic Cell ◽  
Silica Matrix ◽  
High Drug ◽  
Theranostic Agents

Abstract Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ∼87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

Positron emission tomography (PET) with 89Zr-labeled trastuzumab (89Zr-trastuzumab): Monitoring HER2 expression in HER2-positive gastric cancer in vivo.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 35-35
Author(s):  
Y. Y. Janjigian ◽  
N. T. Villegas ◽  
J. P. Holland ◽  
M. A. Shah ◽  
V. Divilov ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Specific Activity ◽  
Gastric Cancer Cell Line ◽  
In Vivo Studies ◽  
In Vitro Assays ◽  
Organ Distribution ◽  
Her2 Positive ◽  
Bibw 2992

35 Background: The ToGA study established HER2 is a target in the treatment of gastric cancer. Trastuzumab pharmacokinetics and organ distribution is varied in each patient and is heavily affected by the extent of tumor load (Oude Munnink, JCO 2010). 89Zr-trastuzumab HER2 PET can be used to image that variability and may aid in detection and staging of HER2-positive tumors. We are implementing 89Zr-radiolabeled trastuzumab PET in vivo for imaging of HER2-positive gastric cancer and for future non-invasive assessment of HER2 inhibition with a dual irreversible HER1/HER2 inhibitor, BIBW-2992. Methods: 89Zr (t1/2 = 3.17 days) was prepared via the 89Y(p,n)89Zr transmutation with high radiochemical yields (1.52±0.11 mCi/μAh) and purity (>99.99%). Trastuzumab was functionalized with the tris-hydroxamate chelate, desferrioxamine B (DFO) and radiolabeled with [89Zr]Zr-oxalate at room temperature. 89Zr-trastuzumab PET experiments in athymic nu/nu mice bearing sub-cutaneous NCI-N87 (HER2+) and/or SNU1 (HER2-) tumors were conducted. NCI-N87 gastric cancer cells were treated with BIBW-2992. Results: 89Zr-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity of 2.82±0.05 mCi/mg. In vitro assays demonstrated >99% radiochemical purity with an immunoreactive fraction of 0.87±7. In vivo biodistribution experiments revealed high and specific uptake in HER2-positive tumors after 72 h (85.2±11.1% ID/g) with retention of activity for over 120 h. No uptake was seen in HER2-negative gastric cancer xenografts. In vitro, BIBW-2992 demonstrates dose dependent growth inhibition in the HER2+ gastric cancer cell line. Conclusions: 89Zr-trastuzumab provides quantitative and highly-specific delineation of HER2-positive gastric cancer. In vivo studies of BIBW2-2992 in gastric cancer with 89Zr-trastuzumab HER2 PET response assessment are underway. A Phase I study of 89Zr-trastuzumab PETin HER2-positive patients is to open at MSKCC imminently. No significant financial relationships to disclose.

scholarly journals 670nm Photobiomodulation Modulates Bioenergetics And Oxidative Stress, Decreasing Inflammatory Mediator Production In An In Vitro Model Of Diabetic Retinopathy

2021 ◽  
Author(s):  
Hannah J. Nonarath ◽  
Alexandria E. Hall ◽  
Gopika SenthilKumar ◽  
Betsy Abroe ◽  
Janis T. Eells ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Near Infrared ◽  
Therapeutic Option ◽  
Model System ◽  
Light Treatment ◽  
Subsequent Increase ◽  
Atp Production

Abstract Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is associated with oxidative stress, nuclear factor-kB (NFkB) activation, and excess production of vascular endothelial growth factor (VEGF) and intracellular adhesion molecule-1 (ICAM-1). Current therapies are invasive, frequently ineffective, and have adverse effects. The application of far-red to near-infrared (NIR) light (630-1000nm) reduces oxidative stress and inflammation in vitro and in vivo. Thus, we hypothesize that 670nm light treatment will dimish oxidative stress preventing downstream inflammatory mechanisms associated with DR. We used an in vitro model system of rat Müller glial cells grown under normal (5 mM) or high (25 mM) glucose conditions and treated with a 670 nm light emitting diode array (LED) (4.5 J/cm2) or no light (sham) daily. We report that a single 670 nm light treatment diminished ROS production and preserved mitochondrial integrity and ATP production in this in vitro model of diabetic retinopathy. Furthermore, treatment for 3 days in culture reduced NFkB activity to levels observed in normal glucose and prevented the subsequent increase in ICAM-1. The ability of 670nm light treatment to prevent early molecular changes in this established DR model system suggests light treatment could become an early therapeutic option for DR.

scholarly journals ROS-Responsive Dimeric Prodrug-Based Nanomedicine Targeted Therapy for Gastric Cancer

2021 ◽  
Author(s):  
Jiachi Ma ◽  
Yuzhong Chen ◽  
Wanqing Liang ◽  
Lei Li ◽  
Jun Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Delivery System ◽  
Inner Core ◽  
Drug Loading ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Novel Approach ◽  
Surface Modified

Abstract Background: Gastric cancer (GC) remains a major public health problem. Ursolic acid (UA) is reported to be effective in inhibiting GC; however, its low solubility and poor biocompatibility have greatly hindered its clinical application. Results: Herein, an innovative ROS-sensitive UA dimeric prodrug is developed by coupling two UA molecules via a ROS-cleavable linkage, which can self-assemble into stable nanoparticles in the presence of surfactant. This new UA-based delivery system comprises the following major components: Ⅰ) dimeric prodrug inner core that can achieve high drug-loading (55%, w/w) and undergo rapid and selective conversion into intact drug molecules in response to ROS; Ⅱ) a polyethylene glycol (PEG) shell to improve colloid stability and extend blood circulation, and Ⅲ) surface-modified iRGD to increase tumor targeting. Conclusion: Enhancement of the antitumor effect of this delivery system was demonstrated against GC tumors in vitro and in vivo. This novel approach offers the potential for clinical applications of UA.

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

scholarly journals Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Ben Liu ◽  
Meng Zhou ◽  
Xiangchun Li ◽  
Xining Zhang ◽  
Qinghua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Androgen Receptor ◽  
Signaling Pathway ◽  
Gender Bias ◽  
Gender Disparity ◽  
Gene Set Enrichment Analysis ◽  
Cancer Type ◽  
Female Patients

AbstractThere is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulate miR-125b expression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.

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