scholarly journals Nanocurcumin-Loaded UCNPs for Cancer Theranostics: Physicochemical Properties, In Vitro Toxicity, and In Vivo Imaging Studies

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2234
Author(s):  
Anbharasi Lakshmanan ◽  
Roman A. Akasov ◽  
Natalya V. Sholina ◽  
Polina A. Demina ◽  
Alla N. Generalova ◽  
...  
Keyword(s):  
Near Infrared ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Laboratory Animals ◽  
In Vitro Toxicity ◽  
Upconversion Nanoparticles ◽  
Lewis Lung Cancer ◽  
Spectral Bands

Formulation of promising anticancer herbal drug curcumin as a nanoscale-sized curcumin (nanocurcumin) improved its delivery to cells and organisms both in vitro and in vivo. We report on coupling nanocurcumin with upconversion nanoparticles (UCNPs) using Poly (lactic-co-glycolic Acid) (PLGA) to endow visualisation in the near-infrared transparency window. Nanocurcumin was prepared by solvent-antisolvent method. NaYF4:Yb,Er (UCNP1) and NaYF4:Yb,Tm (UCNP2) nanoparticles were synthesised by reverse microemulsion method and then functionalized it with PLGA to form UCNP-PLGA nanocarrier followed up by loading with the solvent-antisolvent process synthesized herbal nanocurcumin. The UCNP samples were extensively characterised with XRD, Raman, FTIR, DSC, TGA, UV-VIS-NIR spectrophotometer, Upconversion spectrofluorometer, HRSEM, EDAX and Zeta Potential analyses. UCNP1-PLGA-nanocurcumin exhibited emission at 520, 540, 660 nm and UCNP2-PLGA-nanocurmin showed emission at 480 and 800 nm spectral bands. UCNP-PLGA-nanocurcumin incubated with rat glioblastoma cells demonstrated moderate cytotoxicity, 60–80% cell viability at 0.12–0.02 mg/mL marginally suitable for therapeutic applications. The cytotoxicity of UCNPs evaluated in tumour spheroids models confirmed UCNP-PLGA-nanocurcumin therapeutic potential. As-synthesised curcumin-loaded nanocomplexes were administered in tumour-bearing laboratory animals (Lewis lung cancer model) and showed adequate contrast to enable in vivo and ex vivo study of UCNP-PLGA-nanocurcumin bio distribution in organs, with dominant distribution in the liver and lungs. Our studies demonstrate promise of nanocurcumin-loaded upconversion nanoparticles for theranostics applications.

scholarly journals Efficient Photoacoustic Imaging With Biomimetic Mesoporous Silica-Based Nanoparticles

2021 ◽  
Vol 9 ◽  
Author(s):  
Chuangjia Huang ◽  
Xiaoling Guan ◽  
Hui Lin ◽  
Lu Liang ◽  
Yingling Miao ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Near Infrared ◽  
Ex Vivo ◽  
Photoacoustic Imaging ◽  
Mesoporous Silica Nanoparticles ◽  
Good Biocompatibility ◽  
Targeting Ability ◽  
Body Clearance

Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.

188 DEVELOPMENT OF AN EFFECTIVE WHOLE-OVARY PERFUSION SYSTEM

2015 ◽  
Vol 27 (1) ◽  
pp. 185
Author(s):  
S. Maffei ◽  
G. Galeati ◽  
G. Pennarossa ◽  
T. A. L. Brevini ◽  
G. Gandolfi
Keyword(s):  
Cell Proliferation ◽  
Ex Vivo ◽  
Animal Health ◽  
Basal Medium ◽  
Laboratory Animals ◽  
Large Animal ◽  
Perfusion System ◽  
Whole Ovaries

The different structures of a mammalian ovary require complex 3-dimensional interactions to function properly. It is difficult to access the ovary in vivo and to study its physiology in vitro, it is necessary to dissect its different parts and culture them individually. Although informative, this approach prevents the understanding of the role played by their interactions. Perfusion systems are available for ovaries of laboratory animals while organs of larger species have been maintained in culture only for a few hours. This has prompted us to develop a system that can preserve the function of a whole sheep ovary for a few days ex vivo so that it is available for analysis in controlled conditions. Twenty-four sheep ovaries were collected at the local abattoir; 18 were assigned randomly to 3 experimental groups (media A, B, and C) and 6 were immediately fixed in 10% formaldehyde and used as fresh controls. Whole ovaries were cultured for up to 4 days using a semi-open perfusion system. Organs were perfused through the ovarian artery, at a flow rate of 1.5 mL min–1 with basal medium (M199, 25 mM HEPES, 2 mM l-glutamine and 100 µg mL–1 antibiotic-antimycotic solution) supplemented with 0.4% fatty acid free BSA (medium A); or 0.4% BSA heat shock fraction (medium B); or 10% FBS, 50 ng mL–1 IGF-1, and 50 mg bovine insulin (medium C). Ovaries were stimulated with FSH (Folltropin®-V, Bioniche Animal Health Inc., Belleville, Ontario, Canada) changing medium in a pulsatile manner (1 mg mL–1 for 2 h; 0.5 mg mL–1 for 2 h; 0 mg mL–1 for 20 h), with the same cycle repeated each day of culture. At every change, aliquots were collected for oestradiol (E2) and progesterone (P4) quantification. After culture, ovaries were examined for follicular morphology, cell proliferation, and apoptotic rate. Statistical analysis was performed using one-way ANOVA (SPSS 20, IBM, Armonk, NY, USA). In media A and B, all morphological parameters showed a small but significant decrease compared to fresh control, only after 3 days of culture. The different BSA in medium B did not affect follicle morphology but significantly increased cell proliferation (medium A, 28.59 ± 3.26%; medium B, 32.04 ± 2.67%) and decreased apoptosis (medium A, 32.51 ± 5.92%; medium B, 24.55 ± 2.55%). In both media, steroid concentration increased after FSH pulses (E2 range 1.95–10.50 pg mL–1; P4 range 0.34–3.08 ng mL–1), reaching levels similar to those measurable in peripheral plasma. The presence of FBS, IGF-1, and insulin in medium C allowed extension of the culture period to 4 days with a percentage of intact follicles comparable to that observed after 3 days in media A and B. Moreover, proliferation rates were comparable to fresh controls. Steroid pattern changed with P4 values dropping close to zero (range 0.03–1.18 ng mL–1) and E2 level (range 23.59–94.98 pg mL–1) increasing 10-fold, achieving a concentration similar to that measured in the ovarian vein around oestrous. Our data indicate that it is possible to support viability of large animal whole ovaries for up to 4 days, providing a physiologically relevant model for studying ovarian functions in vitro. Research was supported by AIRC IG 10376 and by the Carraresi Foundation.

IN VIVO NEAR-INFRARED FLUORESCENCE IMAGING OF HUMAN COLON ADENOCARCINOMA BY SPECIFIC IMMUNOTARGETING OF A TUMOR-ASSOCIATED MUCIN

2009 ◽  
Vol 02 (04) ◽  
pp. 407-422 ◽  
Author(s):  
RALPH S. DACOSTA ◽  
YING TANG ◽  
TUULA KALLIOMAKI ◽  
RAYMOND M. REILLY ◽  
ROBERT WEERSINK ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Fluorescence Imaging ◽  
Normal Tissue ◽  
Near Infrared ◽  
Ex Vivo ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Human Colon Adenocarcinoma

Background and Aims: Accurate endoscopic detection of premalignant lesions and early cancers in the colon is essential for cure, since prognosis is closely related to lesion size and stage. Although it has great clinical potential, autofluorescence endoscopy has limited tumor-to-normal tissue image contrast for detecting small preneoplastic lesions. We have developed a molecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate which targets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescence-based endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T) subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivo whole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology. Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours post injection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstrated that modification of CC49 antibodies did not alter their specific tumor-localizing properties, and was antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probe targeting a tumor-associated mucin detects colonic tumors at the molecular level in real time, and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.

scholarly journals Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature-Based Review

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Rajib Hossain ◽  
Cristina Quispe ◽  
Jesús Herrera-Bravo ◽  
Md. Shahazul Islam ◽  
Chandan Sarkar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Human Subjects ◽  
Uterine Cancer ◽  
Safety Data ◽  
Volatile Oil ◽  
Stomach Pain

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: “Lasia spinosa,” then combined with “ethnopharmacological use,” “phytochemistry,” and “pharmacological activity.” This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.

scholarly journals The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Inherited Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Sameh A. Abdelnour ◽  
Long Xie ◽  
Abdallah A. Hassanin ◽  
Erwei Zuo ◽  
Yangqing Lu
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Genetic Diseases ◽  
Patient Specific ◽  
Innovative Technology ◽  
Rna Molecules ◽  
Inherited Diseases ◽  
Genomic Editing

Clustered regularly interspaced short palindromic repeats (CRISPR) is a promising innovative technology for genomic editing that offers scientists the chance to edit DNA structures and change gene function. It has several possible uses consisting of editing inherited deficiencies, treating, and reducing the spread of disorders. Recently, reports have demonstrated the creation of synthetic RNA molecules and supplying them alongside Cas9 into genome of eukaryotes, since distinct specific regions of the genome can be manipulated and targeted. The therapeutic potential of CRISPR/Cas9 technology is great, especially in gene therapy, in which a patient-specific mutation is genetically edited, or in the treating of human disorders that are untreatable with traditional treatments. This review focused on numerous, in vivo, in vitro, and ex vivo uses of the CRISPR/Cas9 technology in human inherited diseases, discovering the capability of this versatile in medicine and examining some of the main limitations for its upcoming use in patients. In addition to introducing a brief impression of the biology of the CRISPR/Cas9 scheme and its mechanisms, we presented the utmost recent progress in the uses of CRISPR/Cas9 technology in editing and treating of human genetic diseases.

A GPC1-targeted and gemcitabine-loaded biocompatible nanoplatform for pancreatic cancer multimodal imaging and therapy

Nanomedicine ◽  
2019 ◽  
Vol 14 (17) ◽  
pp. 2339-2353 ◽  
Author(s):  
Wenli Qiu ◽  
Huifeng Zhang ◽  
Xiao Chen ◽  
Lina Song ◽  
Wenjing Cui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Detection ◽  
Multimodal Imaging ◽  
Near Infrared ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Blood Biochemical

Aim: Biomarker-targeted nanocarrier holds promise for early diagnosis and effective therapy of cancer. Materials & methods: This work successfully designs and evaluates GPC1-targeted, gemcitabine (GEM)-loaded multifunctional gold nanocarrier for near-infrared fluorescence (NIRF)/MRI and targeted chemotherapy against pancreatic cancer in vitro and in vivo. Results: Blood biochemical and histological analyses show that the in vivo toxicity of GPC1-GEM-nanoparticles (NPs) was negligible. Both in vitro and in vivo studies demonstrate that GPC1-GEM-NPs can be used as NIRF/MR contrast agent for pancreatic cancer detection. Treatment of xenografted mice with GPC1-GEM-NPs shows a higher tumor inhibitory effect compared with controls. Conclusion: This novel theranostic nanoplatform provides early diagnostic and effective therapeutic potential for pancreatic cancer.

scholarly journals Effects of wound dressings containing silver on skin and immune cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kristina Nešporová ◽  
Vojtěch Pavlík ◽  
Barbora Šafránková ◽  
Hana Vágnerová ◽  
Pavel Odráška ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ex Vivo ◽  
Wound Dressings ◽  
In Vitro Toxicity ◽  
Skin Cells ◽  
Antimicrobial Efficiency ◽  
Activated Neutrophils ◽  
Stress Related Genes

Abstract Wound dressings with silver have been shown to be cytotoxic in vitro. However, the extrapolation of this cytotoxicity to clinical settings is unclear. We applied dressings with various forms of silver on porcine skin ex vivo and investigated silver penetration and DNA damage. We assessed antimicrobial efficacy, cytotoxicity to skin cells, and immune response induced by the dressings. All dressings elevated the DNA damage marker γ-H2AX and the expression of stress-related genes in explanted skin relative to control. This corresponded with the amount of silver in the skin. The dressings reduced viability, induced oxidative stress and DNA damage in skin cells, and induced the production of pro-inflammatory IL-6 by monocytes. The oxidative burst and viability of activated neutrophils decreased. The amount of silver released into the culture medium varied among the dressings and correlated with in vitro toxicity. However, antimicrobial efficiencies did not correlate strongly with the amount of silver released from the dressings. Antimicrobial efficiency and toxicity are driven by the form of silver and the construction of dressings and not only by the silver concentration. The damaging effects of silver dressings in ex vivo skin highlight the importance of thorough in vivo investigation of silver dressing toxicity.

scholarly journals Targeted photodynamic therapy selectively kills activated fibroblasts in experimental arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (12) ◽  
pp. 3952-3960 ◽  
Author(s):  
Daphne N Dorst ◽  
Mark Rijpkema ◽  
Marti Boss ◽  
Birgitte Walgreen ◽  
Monique M A Helsen ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Synovial Fibroblasts ◽  
Knee Joints ◽  
Specific Cell ◽  
Collagen Induced Arthritis ◽  
Targeted Photodynamic Therapy

Abstract Objective In RA, synovial fibroblasts become activated. These cells express fibroblast activation protein (FAP) and contribute to the pathogenesis by producing cytokines, chemokines and proteases. Selective depletion in inflamed joints could therefore constitute a viable treatment option. To this end, we developed and tested a new therapeutic strategy based on the selective destruction of FAP-positive cells by targeted photodynamic therapy (tPDT) using the anti-FAP antibody 28H1 coupled to the photosensitizer IRDye700DX. Methods After conjugation of IRDye700DX to 28H1, the immunoreactive binding and specificity of the conjugate were determined. Subsequently, tPDT efficiency was established in vitro using a 3T3 cell line stably transfected with FAP. The biodistribution of [111In]In-DTPA-28H1 with and without IRDye700DX was assessed in healthy C57BL/6N mice and in C57BL/6N mice with antigen-induced arthritis. The potential of FAP-tPDT to induce targeted damage was determined ex vivo by treating knee joints from C57BL/6N mice with antigen-induced arthritis 24 h after injection of the conjugate. Finally, the effect of FAP-tPDT on arthritis development was determined in mice with collagen-induced arthritis. Results 28H1-700DX was able to efficiently induce FAP-specific cell death in vitro. Accumulation of the anti-FAP antibody in arthritic knee joints was not affected by conjugation with the photosensitizer. Arthritis development was moderately delayed in mice with collagen-induced arthritis after FAP-tPDT. Conclusion Here we demonstrate the feasibility of tPDT to selectively target and kill FAP-positive fibroblasts in vitro and modulate arthritis in vivo using a mouse model of RA. This approach may have therapeutic potential in (refractory) arthritis.

Abstract 17216: Intracoronary Dual-modal OCT/NIRF Structural-Molecular Imaging with a Clinical Dose of Indocyanine Green (ICG) for Detection of High-risk Coronary Plaques in Diabetic Swine Model

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sunwon Kim ◽  
Min Woo Lee ◽  
Han Saem Cho ◽  
Joon Woo Song ◽  
Sunki Lee ◽  
...  
Keyword(s):  
High Risk ◽  
Near Infrared ◽  
Ex Vivo ◽  
Swine Model ◽  
Fully Integrated ◽  
Coronary Syndrome ◽  
Fibrous Cap ◽  
Nirf Imaging

Background: Acute coronary syndrome is frequently caused by rupture of macrophage abundant plaques with a large lipid-rich core. The present study aimed to investigate whether a fully integrated OCT/NIRF imaging combined with a clinically available near-infrared fluorescence (NIRF) enhancing ICG can detect the inflamed, lipid-rich plaques in swine coronary atheromata whose phenotype is similar to human vulnerable fibroatheroma. Methods and Results: Accelerated atherosclerosis was made by coronary balloon denudation in alloxan induced diabetic minipigs. A rapid coronary imaging (20 mm/sec pullback speed) using a fully integrated OCT/NIRF catheter was safely performed 30 minutes after I.V. injection of ICG (2.0 mg/kg) just under contrast purge. OCT clearly identified the lipid-rich plaques with fibrous cap. Simultaneously acquired, distance-calibrated NIRF imaging detected lipid-laden macrophage signals in OCT-proven plaques (figure). The in vivo plaque target-to-background ratio (pTBR) was significantly higher in ICG-injected swine compared to non-diabetic swines or saline-injected controls (p<0.05), which was validated on ex vivo fluorescence reflectance imaging (FRI) (figure). The in vivo and ex vivo peak pTBRs correlated significantly (p<0.05). In vitro experiments, and histopathology including fluorescence microscopic imaging and immunostaining of the plaque sections corroborated the findings in vivo . Conlusions: An OCT/NIRF imaging with a clinical use of ICG accurately identified macrophage abundant, lipid-rich coronary plaques in diabetic atheromatous minipigs. This highly translatable dual-modal molecular-structural imaging could be relevant for clinical intracoronary detection of high-risk plaques.

FTY720 Abrogates the Therapeutic Potential of Adoptively Transferred Treg Via Inhibition of IL-2 Induced in Vivo Expansion

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2584-2584
Author(s):  
Anna Maria Wolf ◽  
Kathrin Hochegger ◽  
Robert Zeiser ◽  
Christoph Duerr ◽  
Michael Sixt ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Transfer ◽  
Chemokine Receptors ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Effective Means ◽  
Effector T Cells ◽  
Target Tissue

Abstract CD4+CD25+ T cells (Treg) entry into secondary lymphoid organs (SLO) and local expansion after activation is at least in part responsible for their immunosuppressive action. Thus we hypothesized that trapping of adoptively transferred Treg in SLO would be an effective means to tip the balance towards a more immunosuppressive milieu within the LN microenvironment. Systemic application of the sphingosine-phosphate receptor agonist FTY720 has been proven to trap harmful effector T cells in SLO, thereby inhibiting their migration and destruction of target tissue. Here we provide first evidence that selective entrapment of adoptively transferred Treg in inflammatory LN can be achieved by blockade of SP-receptors upon ex vivo exposure of Treg to FTY720 before adoptive transfer. FTY720 exposure did not interfere with proper Treg localization within the T-cell areas of SLO as determined by immunofluorescent microscopy after co-transfer of either FTY720- or solvent exposed and subsequently differentially labelled Treg. However, despite the fact that the in vitro phenotype (including expression of adhesion and chemokine receptors), function (including anergy and suppressive activity) and survival (determined by Annexin/PI staining) of Treg remained unaltered by FTY720, it abrogated their protective effect after adoptive transfer in a murine model of acute experimental glomerulonephritis (determined by quantification of proteinuria and histological analysis) as well as in an acute GvHD model (determined by survival analysis and quantification of the in vivo expansion of luciferase-transgenic effector T cells by bioluminiscence technology). Notably, adoptive transfer of CFSE-labelled Treg revealed a markedly impaired proliferation of Treg in inflammatory SLO when pre-exposed to FTY720 ex vivo. Accordingly, FTY720 blocked Treg-proliferation induced by TCR-stimulation in combination with IL-2 in vitro. In line with this observation, FTY720 completely abolishes IL-2 induced phosphorylation of STAT-5. Thus, SP-1P receptors induce Treg trapping in inflammatory SLO but abrogate their in vivo immunosuppressive potential by inhibition of local Treg expansion.

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