scholarly journals Tumor Targeting: A Strategy for Tumor Targeting by Higher‐Order Glycan Pattern Recognition: Synthesis and In Vitro and In Vivo Properties of Glycoalbumins Conjugated with Four Different N ‐Glycan Molecules (Small 46/2020)

Small ◽  
2020 ◽  
Vol 16 (46) ◽  
pp. 2070253
Author(s):  
Ivan Smirnov ◽  
Regina Sibgatullina ◽  
Sayaka Urano ◽  
Tsuyoshi Tahara ◽  
Peni Ahmadi ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Tumor Targeting ◽  
Higher Order ◽  
Glycan Pattern

A Strategy for Tumor Targeting by Higher‐Order Glycan Pattern Recognition: Synthesis and In Vitro and In Vivo Properties of Glycoalbumins Conjugated with Four Different N ‐Glycan Molecules

Small ◽  
2020 ◽  
Vol 16 (46) ◽  
pp. 2004831
Author(s):  
Ivan Smirnov ◽  
Regina Sibgatullina ◽  
Sayaka Urano ◽  
Tsuyoshi Tahara ◽  
Peni Ahmadi ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Tumor Targeting ◽  
Higher Order ◽  
Glycan Pattern

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

scholarly journals Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 314
Author(s):  
Maria D. Dmitrieva ◽  
Anna A. Voitova ◽  
Maya A. Dymova ◽  
Vladimir A. Richter ◽  
Elena V. Kuligina
Keyword(s):  
Phage Display ◽  
Cell Sorting ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Search Strategy ◽  
Tumor Therapy ◽  
Therapeutic Agents ◽  
Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

scholarly journals Atovaquone-HSA nano-drugs enhance the efficacy of PD-1 blockade immunotherapy by alleviating hypoxic tumor microenvironment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Simeng Wang ◽  
Xinrui Zhou ◽  
Zekun Zeng ◽  
Mengjun Sui ◽  
Lihong Chen ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Disulfide Bonds ◽  
Tumor Targeting ◽  
Tumor Hypoxia ◽  
Animal Experiments ◽  
Complex Iii ◽  
Mitochondrial Activity ◽  
Hypoxic Tumor

Abstract Background Hypoxia is inherent character of most solid malignancies, leading to the failure of chemotherapy, radiotherapy and immunotherapy. Atovaquone, an anti-malaria drug, can alleviate tumor hypoxia by inhibiting mitochondrial complex III activity. The present study exploits atovaquone/albumin nanoparticles to improve bioavailability and tumor targeting of atovaquone, enhancing the efficacy of anti-PD-1 therapy by normalizing tumor hypoxia. Methods We prepared atovaquone-loaded human serum albumin (HSA) nanoparticles stabilized by intramolecular disulfide bonds, termed HSA-ATO NPs. The average size and zeta potential of HSA-ATO NPs were measured by particle size analyzer. The morphology of HSA-ATO NPs was characterized by transmission electron microscope (TEM). The bioavailability and safety of HSA-ATO NPs were assessed by animal experiments. Flow cytometry and ELISA assays were used to evaluate tumor immune microenvironment. Results Our data first verified that atovaquone effectively alleviated tumor hypoxia by inhibiting mitochondrial activity both in vitro and in vivo, and successfully encapsulated atovaquone in vesicle with albumin, forming HSA-ATO NPs of approximately 164 nm in diameter. We then demonstrated that the HSA-ATO NPs possessed excellent bioavailability, tumor targeting and a highly favorable biosafety profile. When combined with anti-PD-1 antibody, we observed that HSA-ATO NPs strongly enhanced the response of mice bearing tumor xenografts to immunotherapy. Mechanistically, HSA-ATO NPs promoted intratumoral CD8+ T cell recruitment by alleviating tumor hypoxia microenvironment, thereby enhancing the efficacy of anti-PD-1 immunotherapy. Conclusions Our data provide strong evidences showing that HSA-ATO NPs can serve as safe and effective nano-drugs to enhance cancer immunotherapy by alleviating hypoxic tumor microenvironment. Graphic abstract

scholarly journals Artificial Neural Network in Drug Delivery and Pharmaceutical Research

2013 ◽  
Vol 7 (1) ◽  
pp. 49-62 ◽  
Author(s):  
Vijaykumar Sutariya ◽  
Anastasia Groshev ◽  
Prabodh Sadana ◽  
Deepak Bhatia ◽  
Yashwant Pathak
Keyword(s):  
Neural Network ◽  
Neural Networks ◽  
Drug Delivery ◽  
Pattern Recognition ◽  
Analytical Data ◽  
Pharmaceutical Research ◽  
Artificial Neural ◽  
The Brain

Artificial neural networks (ANNs) technology models the pattern recognition capabilities of the neural networks of the brain. Similarly to a single neuron in the brain, artificial neuron unit receives inputs from many external sources, processes them, and makes decisions. Interestingly, ANN simulates the biological nervous system and draws on analogues of adaptive biological neurons. ANNs do not require rigidly structured experimental designs and can map functions using historical or incomplete data, which makes them a powerful tool for simulation of various non-linear systems.ANNs have many applications in various fields, including engineering, psychology, medicinal chemistry and pharmaceutical research. Because of their capacity for making predictions, pattern recognition, and modeling, ANNs have been very useful in many aspects of pharmaceutical research including modeling of the brain neural network, analytical data analysis, drug modeling, protein structure and function, dosage optimization and manufacturing, pharmacokinetics and pharmacodynamics modeling, and in vitro in vivo correlations. This review discusses the applications of ANNs in drug delivery and pharmacological research.

scholarly journals Chimeric CLL-1 Antibody Fusion Proteins Containing Granulocyte-Macrophage Colony-Stimulating Factor or Interleukin-2 With Specificity for B-Cell Malignancies Exhibit Enhanced Effector Functions While Retaining Tumor Targeting Properties

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4437-4447 ◽  
Author(s):  
Jason L. Hornick ◽  
Leslie A. Khawli ◽  
Peisheng Hu ◽  
Maureen Lynch ◽  
Peter M. Anderson ◽  
...  
Keyword(s):  
B Cell ◽  
Fusion Proteins ◽  
Tumor Targeting ◽  
B Cell Malignancies ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Although monoclonal antibody (MoAb) therapy of the human malignant lymphomas has shown success in clinical trials, its full potential for the treatment of hematologic malignancies has yet to be realized. To expand the clinical potential of a promising human-mouse chimeric antihuman B-cell MoAb (chCLL-1) constructed using the variable domains cloned from the murine Lym-2 (muLym-2) hybridoma, fusion proteins containing granulocyte-macrophage colony-stimulating factor (GM-CSF) (chCLL-1/GM–CSF) or interleukin (IL)-2 (chCLL-1/IL–2) were generated and evaluated for in vitro cytotoxicity and in vivo tumor targeting. The glutamine synthetase gene amplification system was employed for high level expression of the recombinant fusion proteins. Antigenic specificity was confirmed by a competition radioimmunoassay against ARH-77 human myeloma cells. The activity of chCLL-1/GM–CSF was established by a colony formation assay, and the bioactivity of chCLL-1/IL–2 was confirmed by supporting the growth of an IL-2–dependent T-cell line. Antibody-dependent cellular cytotoxicity against ARH-77 target cells demonstrated that both fusion proteins mediate enhanced tumor cell lysis by human mononuclear cells. Finally, biodistribution and imaging studies in nude mice bearing ARH-77 xenografts indicated that the fusion proteins specifically target the tumors. These in vitro and in vivo data suggest that chCLL-1/GM–CSF and chCLL-1/IL–2 have potential as immunotherapeutic reagents for the treatment of B-cell malignancies.

scholarly journals Strains, Mechanism, and Perspective:Salmonella-Based Cancer Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Cheng-Zhi Wang ◽  
Robert A. Kazmierczak ◽  
Abraham Eisenstark
Keyword(s):  
Synthetic Biology ◽  
Tumor Targeting ◽  
Tumor Therapy ◽  
The Other ◽  
Cancer Therapies ◽  
Chemotherapeutic Drugs ◽  
Serovar Typhimurium ◽  
Candidate Strain

Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such asSalmonella,Listeria,Escherichia, andClostridiumhave proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeuticSalmonellamodels, the most intensively studied bacterial genus in this field. One of theseSalmonellamodels is ourSalmonella entericaserovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypesin vitroandin vivo, and what is currently known about the mechanisms by which they target and destroy tumors.

Breast Tumor Targeting with PAMAM-PEG-5FU-99mTc As a New Therapeutic Nanocomplex: In In-vitro and In-vivo studies

2020 ◽  
Vol 22 (2) ◽  
Author(s):  
Asghar Narmani ◽  
Monire Alsadat Afzali Arani ◽  
Javad Mohammadnejad ◽  
Ali Zaman Vaziri ◽  
Sedigheh Solymani ◽  
...  
Keyword(s):  
Breast Tumor ◽  
Tumor Targeting ◽  
In Vivo Studies

A self-delivery system based on an amphiphilic proapoptotic peptide for tumor targeting therapy

2019 ◽  
Vol 7 (5) ◽  
pp. 778-785 ◽  
Author(s):  
Si Chen ◽  
Jin-Xuan Fan ◽  
Xin-Hua Liu ◽  
Ming-Kang Zhang ◽  
Fan Liu ◽  
...  
Keyword(s):  
Delivery System ◽  
Therapeutic Efficacy ◽  
Tumor Targeting ◽  
Targeting Therapy

A self-delivery system KDH was constructed to realize tumor targeting therapy, and it possessed extraordinary therapeutic efficacy both in vitro and in vivo.

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