DEVELOPMENT OF A PHOTOSENSITIZER DELIVERY SYSTEM FOR THERAPY AND DIAGNOSTICS IN ONCOLOGY

2020 ◽  
pp. 124-125
Author(s):  
A.Semkina Semkina ◽  
M.Abakumov Abakumov ◽  
P.Ostroverkhov Ostroverkhov ◽  
M. Grin
Keyword(s):  
Photodynamic Therapy ◽  
Physicochemical Properties ◽  
Tumor Cells ◽  
Therapeutic Effect ◽  
Delivery System ◽  
Biological Studies ◽  
Kinetics Of ◽  
Ct26 Tumor

In this work, the MNP-HSA-PEG-PS@4 complex was obtained and its physicochemical properties were studied. Biological studies have also been conducted. Namely, the ability of the drug to accumulate in CT26 tumor cells in vitro and the kinetics of drug accumulation in the tumor in vivo were studied. Then, the effectiveness of photodynamic therapy was studied under different conditions. The maximum therapeutic effect was achieved with irradiation at 1 hour after injection of the drug.

scholarly journals A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer

2021 ◽  
Vol 118 (13) ◽  
pp. e2012748118
Author(s):  
Lingfan Xu ◽  
Yu Yin ◽  
Yanjing Li ◽  
Xufeng Chen ◽  
Yan Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Tumor Cells ◽  
Therapeutic Effect ◽  
Hormonal Therapy ◽  
Therapy Resistance ◽  
Therapeutic Resistance ◽  
Switch Mechanism

Cellular metabolism in cancer is significantly altered to support the uncontrolled tumor growth. How metabolic alterations contribute to hormonal therapy resistance and disease progression in prostate cancer (PCa) remains poorly understood. Here we report a glutaminase isoform switch mechanism that mediates the initial therapeutic effect but eventual failure of hormonal therapy of PCa. Androgen deprivation therapy inhibits the expression of kidney-type glutaminase (KGA), a splicing isoform of glutaminase 1 (GLS1) up-regulated by androgen receptor (AR), to achieve therapeutic effect by suppressing glutaminolysis. Eventually the tumor cells switch to the expression of glutaminase C (GAC), an androgen-independent GLS1 isoform with more potent enzymatic activity, under the androgen-deprived condition. This switch leads to increased glutamine utilization, hyperproliferation, and aggressive behavior of tumor cells. Pharmacological inhibition or RNA interference of GAC shows better treatment effect for castration-resistant PCa than for hormone-sensitive PCa in vitro and in vivo. In summary, we have identified a metabolic function of AR action in PCa and discovered that the GLS1 isoform switch is one of the key mechanisms in therapeutic resistance and disease progression.

scholarly journals Precision Nanomedicine Vol. 1, Issue 3, Table of Contents

2018 ◽  
Vol 1 (3) ◽  
Keyword(s):  
Pancreatic Cancer ◽  
Cervical Cancer ◽  
Tumor Cells ◽  
Delivery System ◽  
Complement Activation ◽  
Sol Gel ◽  
Therapeutic Vaccine ◽  
Basic Research

Prec. Nanomed. 2018 Oct;1(3):183-193. BASIC RESEARCH From the Clinical Editor: The number of women affected by cervical cancer worldwide is very significant and the disease is associated with human papilloma virus (HPV) infection. Although the use of HPV vaccines has proven to be useful in disease protection, they only work in women who have never been infected by HPV previously. Thus, the development of a therapeutic vaccine that targets HPV-infected cells is needed for women who are already infected with the virus. In this study, the authors describe the use of a self-adjuvating polymer-based delivery system for the development of a therapeutic vaccine. Therefore, while efforts are progressing, vaccine candidates are still required against late stage cervical cancer via improving the vaccine delivery system. Authors demonstrate that the combination of polymer-based and liposome delivery systems may be effective without the use of additional adjuvant and with just a single dose immunization. This finding has potential importance for other cancer vaccines as well. Prec. Nanomed. 2018 Oct;1(3):173-182 POTENTIAL CLINICAL SIGNIFICANCE From the Clinical Editor: The treatment of triple-negative breast cancer is often difficult due to frequent resistance to doxorubicin. Using different nano-formulations based on sol-gel technology to encapsulate doxorubicin, the authors here showed enhanced dose-response metrics and tumor cell kill of these cancer cells due to an increased drug accumulation in the local tumor environment. This platform shows early promise in terms of eventual clinical translatability. Prec. Nanomed. 2018 Oct;1(3):194-207. BASIC RESEARCH From the Clinical Editor: Surgical resection remains the main treatment modality for pancreatic cancer. Thus, the ability to delineate the tumor accurately during operation is important to ensure all tumor cells are resected. Here, the authors describe the development of a multimodal imaging probe using nanospheres to target epithelial cells of pancreatic cancer. The specificity to target only tumor cells was clearly shown in both in-vitro and in-vivo experiments. This technology may provide a new fluorescence imaging technique to help the field of surgical oncology in the future. Prec. Nanomed. 2018 Oct;1(3):208-217. BASIC RESEARCH From the Clinical Editor: Preclinical characterization of nanotechnology-based products is essential for translating innovative applications into clinics. In addition to the innate immune system complement activation plays an important role in regulating the adaptive immune response. Undesirable activation of the complement system in response to new composites may lead to hypersensitivity reactions. The authors describe the importance of mouse strain selection for in vitro complement activation analysis addressing also the existence of inter- and intraspecies variability.

A folic acid conjugated polyethylenimine-modified PEGylated nanographene loaded photosensitizer: photodynamic therapy and toxicity studies in vitro and in vivo

2016 ◽  
Vol 4 (12) ◽  
pp. 2190-2198 ◽  
Author(s):  
Yi-Ping Zeng ◽  
Sheng-Lin Luo ◽  
Zhang-You Yang ◽  
Jia-Wei Huang ◽  
Hong Li ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Folic Acid ◽  
Delivery System ◽  
Tumor Targeting ◽  
Therapy Efficacy ◽  
Toxicity Studies ◽  
Targeting Delivery

A novel nanographene-based tumor-targeting delivery system has high photodynamic therapy efficacy with no obvious toxicity and could potentially be utilized in biomedicine.

A delivery system to avoid self-aggregation and to improve in vitro and in vivo skin delivery of a phthalocyanine derivative used in the photodynamic therapy

2011 ◽  
Vol 155 (3) ◽  
pp. 400-408 ◽  
Author(s):  
Fábia Cristina Rossetti ◽  
Luciana Biagini Lopes ◽  
Aline Regina H. Carollo ◽  
José A. Thomazini ◽  
Antônio Cláudio Tedesco ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Delivery System ◽  
Skin Delivery ◽  
Phthalocyanine Derivative ◽  
Self Aggregation

scholarly journals Antimalarial Drugs Enhance the Cytotoxicity of 5-Aminolevulinic Acid-Based Photodynamic Therapy against the Mammary Tumor Cells of Mice In Vitro

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3891 ◽  
Author(s):  
Tomohiro Osaki ◽  
Kiwamu Takahashi ◽  
Masahiro Ishizuka ◽  
Tohru Tanaka ◽  
Yoshiharu Okamoto
Keyword(s):  
Photodynamic Therapy ◽  
Tumor Cells ◽  
Mammary Tumor ◽  
Aminolevulinic Acid ◽  
Annexin V ◽  
Resistant Cell ◽  
Mammary Tumor Cells ◽  
Radiation Resistant

Artemisinin and its derivatives, including artesunate (ART) and artemether (ARM), exert anticancer effects in the micromolar range in drug and radiation-resistant cell lines. Artemisinin has been reported to sensitize cervical cancer cells to radiotherapy. In the present study, we determined whether ART and ARM could enhance the cytotoxicity of 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) against the mammary tumor cells of mice. The corrected PpIX fluorescence intensities in the control, 5-ALA, 5-ALA + ART, and 5-ALA + ARM groups were 3.385 ± 3.730, 165.7 ± 33.45, 139.0 ± 52.77, and 165.4 ± 51.10 a.u., respectively. At light doses of 3 and 5 J/cm2, the viability of 5-ALA-PDT-treated cells significantly decreased with ART (p < 0.01 and p < 0.01) and ARM treatment (p < 0.01 and p < 0.01). Besides, the number of annexin V-FITC and ethidium homodimer III-positive cells was greater in the 5-ALA-PDT with ARM group than that in the other groups. N-acetylcysteine could not significantly inhibit the percentages of apoptotic cells or inviable cells induced by 5-ALA-PDT with ARM. These reactive oxygen species-independent mechanisms might enhance cytotoxicity in 5-ALA-PDT with ARM-treated tumor cells, suggesting that the use of 5-ALA-PDT with ARM could be a new strategy to enhance PDT cytotoxicity against tumor cells. However, as these results are only based on in vitro studies, further in vivo investigations are required.

Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: In vitro and in vivo studies

2015 ◽  
Vol 12 (1) ◽  
pp. 98-107 ◽  
Author(s):  
Thierllen Barroso Graciano ◽  
Tatielle Soares Coutinho ◽  
Camila Beatriz Cressoni ◽  
Cristhiane de Paula Freitas ◽  
Maria Bernadete Riemma Pierre ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Delivery System ◽  
Toluidine Blue ◽  
In Vivo Studies

scholarly journals A recombinant oncolytic Newcastle virus expressing MIP-3α promotes systemic antitumor immunity

2020 ◽  
Vol 8 (2) ◽  
pp. e000330
Author(s):  
Feng-Ying Huang ◽  
Jin-Yan Wang ◽  
Shu-Zhen Dai ◽  
Ying-Ying Lin ◽  
Yan Sun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Adoptive Transfer ◽  
Intratumoral Injection ◽  
T Cell Subsets ◽  
Dc Vaccine ◽  
Ct26 Tumor

BackgroundThe oncolytic Newcastle disease virus (NDV) is inherently able to trigger the lysis of tumor cells and induce the immunogenic cell death (ICD) of tumor cells and is also an excellent gene-engineering vector. The macrophage inflammatory protein-3α (MIP-3α) is a specific chemokine for dendritic cells (DCs). Thus, we constructed a recombinant NDV expressing MIP-3α (NDV-MIP3α) as an in vivo DC vaccine for amplifying antitumor immunities.MethodsThe recombinant NDV-MIP3α was constructed by the insertion of MIP-3α cDNA between the P and M genes. Western blotting assay and ELISA were used to detect MIP-3α, HMGB1, IgG, and ATP in the supernatant and sera. The chemotaxis of DCs was examined by Transwell chambers. The phenotypes of the immune cells (eg, DCs) were analyzed by flow cytometry. The antitumor efficiency of NDV-MIP3α was observed in B16 and CT26 tumor-bearing mice. Immunofluorescence and immunohistochemistry were applied to observe the ecto-calreticulin (CRT) and intratumoral attraction of DCs. Adoptive transfer of splenocytes and antibodies and depletion of T-cell subsets were used to evaluate the relationship between antitumor immunities and the role of the T-cell subtype.ResultsThe findings show that NDV-MIP3α has almost the same capabilities of tumor lysis and induction of ICD as the wild-type NDV (NDV-WT). MIP-3α secreted by NDV-MIP3α could successfully attract DCs in vitro and in vivo. Both B16 and CT26 cells infected with NDV-MIP3α could strongly promote DC maturation and activation. Compared with NDV-WT, intratumoral injection of NDV-MIP3α and the adoptive transfer of T lymphocytes from mice injected with NDV-MIP3α resulted in a significant suppression of B16 and CT26 tumor growth. The NDV-MIP3α-induced production of tumor-specific cellular and humoral immune responses was dependent on CD8+ T cells and partially on CD4+ T cells. A significant reversion of tumor microenvironments was found in the mice injected with NDV-MIP3α.ConclusionsCompared with NDV-WT, the recombinant NDV-MIP3α as an in vivo DC vaccine demonstrates enhanced antitumor activities through the induction of stronger system immunities and modulation of the tumor microenvironment. This strategy may be a potential approach for the generation of an in vivo DC vaccine.

scholarly journals In vitro and in vivo matrix metalloproteinase expression after photodynamic therapy with a liposomal formulation of aminolevulinic acid and its methyl ester

2010 ◽  
Vol 15 (4) ◽  
Author(s):  
Beata Osiecka ◽  
Kamil Jurczyszyn ◽  
Krzysztof Symonowicz ◽  
Andrzej Bronowicz ◽  
Paweł Ostasiewicz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Methyl Ester ◽  
Tumor Cells ◽  
Aminolevulinic Acid ◽  
Malignant Tumors ◽  
Single Cells ◽  
Liposomal Formulation ◽  
Tumor Bearing

AbstractPhotodynamic therapy (PDT) is a well-known method for the treatment of malignant tumors, and its principles have been well established over the past 30 years. This therapy involves the application of a chemical called a photosensitizer and its subsequent excitation with light at the appropriate wavelength and energy. Topical photodynamic therapy with aminolevulinic acid (5-ALA) is an alternative therapy for many malignant processes, including nonmelanoma skin cancers such as basal-cell carcinoma (BCC). Our novel approach for this study was to use a liposomal formulation of 5-ALA and its methyl ester (commercially available as metvix) both in vitro and in vivo, and to check whether the liposome-entrapped precursors of photosensitizers can induce the expression of metalloproteinases (MMPs) in animal tumor cells and in other tissues from tumor-bearing rats and in selected cell lines in vitro. We also checked whether the application of tissue inhibitors of matrix metalloproteinases (TIMPs) has any effect on MMPs in the above-mentioned experimental models, and if they can cause complete inhibition of MMP expression. Immunohistochemical studies revealed that after the PDT, the intensity of expression of MMPs in healthy animals was very low and seen in single cells only. After the PDT in tumor-bearing rats, MMP-3 was expressed in the tumor cells with the highest intensity of staining in the tissues directly adjacent to the tumors, while MMP-2 and -9 were not found. In the control groups, there was no observed expression of MMPs. In vitro studies showed that MMP-3 was expressed in MCF-7 cells after PDT, but MMP-9 was not observed and MMP-2 was only seen in single cases. Our studies confirmed that the application of an MMP-3 inhibitor may block an induction of MMP-3 expression which had previously been initiated by PDT. The preliminary data obtained from cancer patients revealed that new precursors are effective in terms of PDT, and that using MMP inhibitors should be considered as a potential enhancing factor in clinical PDT.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

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