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  1. Article ; Online: Nanoindentation study of the viscoelastic properties of human triple negative breast cancer tissues: Implications for mechanical biomarkers.

    Ezenwafor, Theresa / Anye, Vitalis / Madukwe, Jonathan / Amin, Said / Obayemi, John / Odusanya, Olushola / Soboyejo, Winston

    Acta biomaterialia

    2023  Volume 158, Page(s) 374–392

    Abstract: This paper presents the results of a combined experimental and theoretical study of the structure and viscoelastic properties of human non-tumorigenic mammary breast tissues and triple negative breast cancer (TNBC) tissues of different histological ... ...

    Abstract This paper presents the results of a combined experimental and theoretical study of the structure and viscoelastic properties of human non-tumorigenic mammary breast tissues and triple negative breast cancer (TNBC) tissues of different histological grades. A combination of immunofluorescence and confocal microscopy, and atomic force microscopy is used to study the actin cytoskeletal structures of non-tumorigenic and tumorigenic breast tissues (grade I to grade III). A combination of nanoindentation and statistical techniques is then used to measure viscoelastic properties of non-tumorigenic and human TNBC of different histological grades. A Standard Fluid Model/Anti-Zener Model II is also used to characterize the viscoelastic properties of the non-tumorigenic and tumorigenic TNBC tissues of different grades. The implications of the results are discussed for the potential application of nanoindentation and statistical deconvolution techniques to the development of mechanical biomarkers for TNBC detection/cancer diagnosis. STATEMENT OF SIGNIFICANCE: There is increasing interest in the development of mechanical biomarkers for cancer diagnosis. Here, we show that nanoindentation techniques can be used to characterize the viscoelastic properties of normal breast tissue and TNBC tissues of different histological grades. The Standard Fluid Model (Anti-Zener Model II) is used to classify the viscoelastic properties of breast tissues of different TNBC histological grades. Our results suggest that breast tissue and TNBC tissue viscoelastic properties can be used as mechanical biomarkers for the detection of TNBC at different stages.
    MeSH term(s) Humans ; Triple Negative Breast Neoplasms/pathology ; Breast ; Biomarkers, Tumor ; Cytoskeleton
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2023-01-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2023.01.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Actin cytoskeletal structure and the statistical variations of the mechanical properties of non-tumorigenic breast and triple-negative breast cancer cells.

    Onwudiwe, Killian / Hu, Jingjie / Obayemi, John / Uzonwanne, Vanessa / Ani, Chukwuemeka / Nwazojie, Chukwudalu / Onyekanne, Chinyerem / Ezenwafor, Theresa / Odusanya, Olushola / Soboyejo, Winston

    Journal of the mechanical behavior of biomedical materials

    2021  Volume 119, Page(s) 104505

    Abstract: This paper presents the results of a study of the actin cytoskeletal structures and the statistical variations in the actin fluorescence intensities and viscoelastic properties of non-tumorigenic breast cells and triple-negative breast cancer cells at ... ...

    Abstract This paper presents the results of a study of the actin cytoskeletal structures and the statistical variations in the actin fluorescence intensities and viscoelastic properties of non-tumorigenic breast cells and triple-negative breast cancer cells at different stages of tumor progression. The variation in the actin content of the cell cytoskeletal structures is shown to be consistent with the viscoelastic properties of the cell as it progresses from non-tumorigenic to more metastatic states. The corresponding viscoelastic properties of the nuclei and the cytoplasm (Young's moduli, viscosities, and relaxation times) of the cells are also measured using Digital Image Correlation (DIC) and shear assay techniques. These properties are shown to exhibit statistical variations that are well characterized by normal distributions. The changes in the mean properties of individual cancer cells are tested using Fisher pairwise comparisons and the analysis of variance (ANOVA). The implications of the results are then discussed for the development of shear assay techniques and mechanical biomarkers for the detection of triple-negative breast cancer at different stages of tumor progression.
    MeSH term(s) Actins ; Cytoskeleton ; Elastic Modulus ; Humans ; Triple Negative Breast Neoplasms ; Viscosity
    Chemical Substances Actins
    Language English
    Publishing date 2021-04-09
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2378381-3
    ISSN 1878-0180 ; 1751-6161
    ISSN (online) 1878-0180
    ISSN 1751-6161
    DOI 10.1016/j.jmbbm.2021.104505
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Adhesion of LHRH/EphA2 to human Triple Negative Breast Cancer tissues.

    Ezenwafor, Theresa C / Uzonwanne, Vanessa O / Madukwe, Jonathan U A / Amin, Said M / Anye, Vitalis C / Obayemi, John D / Odusanya, Olushola S / Soboyejo, Winston O

    Journal of the mechanical behavior of biomedical materials

    2022  Volume 136, Page(s) 105461

    Abstract: The adhesive interactions between molecular recognition units (such as specific peptides and antibodies) and antigens or other receptors on the surfaces of tumors are of great value in the design of targeted nanoparticles and drugs for the detection and ... ...

    Abstract The adhesive interactions between molecular recognition units (such as specific peptides and antibodies) and antigens or other receptors on the surfaces of tumors are of great value in the design of targeted nanoparticles and drugs for the detection and treatment of specific cancers. In this paper, we present the results of a combined experimental and theoretical study of the adhesion between Luteinizing Hormone Releasing Hormone (LHRH)/Epherin type A2 (EphA2)-AFM coated tips and LHRH/EphA2 receptors that are overexpressed on the surfaces of human Triple Negative Breast Cancer (TNBC) tissues of different histological grades. Following a histochemical and immuno-histological study of human tissue extracts, the receptor overexpression, and their distributions are characterized using Immunohistochemistry (IHC), Immunofluorescence (IF), and a combination of fluorescence microscopy and confocal microscopy. The adhesion forces between LHRH or EphA2 and human TNBC breast tissues are measured using force microscopy techniques that account for the potential effects of capillary forces due to the presence of water vapor. The corresponding adhesion energies are also determined using adhesion theory. The pull off forces and adhesion energies associated with higher grades of TNBC are shown to be greater than those associated with normal/non-tumorigenic human breast tissues, which were studied as controls. The observed increase in adhesion forces and adhesion energies are also correlated with the increasing incidence of LHRH/EphA2 receptors at higher grades of TNBC. The implications of the results are discussed for the development of targeted nanostructures for the detection and treatment of TNBC.
    MeSH term(s) Humans ; Cell Line, Tumor ; Gonadotropin-Releasing Hormone/chemistry ; Nanoparticles ; Receptors, LHRH/chemistry ; Triple Negative Breast Neoplasms/pathology
    Chemical Substances Gonadotropin-Releasing Hormone (33515-09-2) ; Receptors, LHRH
    Language English
    Publishing date 2022-09-17
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2378381-3
    ISSN 1878-0180 ; 1751-6161
    ISSN (online) 1878-0180
    ISSN 1751-6161
    DOI 10.1016/j.jmbbm.2022.105461
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Laser-induced heating of polydimethylsiloxane-magnetite nanocomposites for hyperthermic inhibition of triple-negative breast cancer cell proliferation.

    Onyekanne, Chinyerem E / Salifu, Ali A / Obayemi, John D / Ani, Chukwuemeka J / Ashouri Choshali, Habibeh / Nwazojie, Chukwudalu C / Onwudiwe, Killian C / Oparah, Josephine C / Ezenwafor, Theresa C / Ezeala, Chukwudi C / Odusanya, Olushola S / Rahbar, Nima / Soboyejo, Winston O

    Journal of biomedical materials research. Part B, Applied biomaterials

    2022  Volume 110, Issue 12, Page(s) 2727–2743

    Abstract: This paper presents the results of an experimental and computational study of the effects of laser-induced heating provided by magnetite nanocomposite structures that are being developed for the localized hyperthermic treatment of triple-negative breast ... ...

    Abstract This paper presents the results of an experimental and computational study of the effects of laser-induced heating provided by magnetite nanocomposite structures that are being developed for the localized hyperthermic treatment of triple-negative breast cancer. Magnetite nanoparticle-reinforced polydimethylsiloxane (PDMS) nanocomposites were fabricated with weight percentages of 1%, 5%, and 10% magnetite nanoparticles. The nanocomposites were exposed to incident Near Infrared (NIR) laser beams with well-controlled powers. The laser-induced heating is explored in: (i) heating liquid media (deionized water and cell growth media [Leibovitz L15+]) to characterize the photothermal properties of the nanocomposites, (ii) in vitro experiments that explore the effects of localized heating on triple-negative breast cancer cells, and (iii) experiments in which the laser beams penetrate through chicken tissue to heat up nanocomposite samples embedded at different depths beneath the chicken skin. The resulting plasmonic laser-induced heating is explained using composite theories and heat transport models. The results show that the laser/nanocomposite interactions decrease the viability of triple-negative breast cancer cells (MDA-MB-231) at temperatures in the hyperthermia domain between 41 and 44°C. Laser irradiation did not cause any observed physical damage to the chicken tissue. The potential in vivo performance of the PDMS nanocomposites was also investigated using computational finite element models of the effects of laser/magnetite nanocomposite interactions on the temperatures and thermal doses experienced by tissues that surround the nanocomposite devices. The implications of the results are then discussed for the development of implantable nanocomposite devices for localized treatment of triple-negative breast cancer tissue via hyperthermia.
    MeSH term(s) Cell Line, Tumor ; Cell Proliferation ; Dimethylpolysiloxanes ; Ferrosoferric Oxide/chemistry ; Heating ; Humans ; Hyperthermia, Induced/methods ; Lasers ; Nanocomposites/chemistry ; Triple Negative Breast Neoplasms/therapy ; Water
    Chemical Substances Dimethylpolysiloxanes ; Water (059QF0KO0R) ; baysilon (63148-62-9) ; Ferrosoferric Oxide (XM0M87F357)
    Language English
    Publishing date 2022-07-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2099992-6
    ISSN 1552-4981 ; 1552-4973 ; 0021-9304
    ISSN (online) 1552-4981
    ISSN 1552-4973 ; 0021-9304
    DOI 10.1002/jbm.b.35124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sustained release of alpha-methylacyl-CoA racemase (AMACR) antibody-conjugated and free doxorubicin from silica nanoparticles for prostate cancer cell growth inhibition.

    Aina, Toyin / Salifu, Ali A / Kizhakkepura, Sonu / Danyuo, Yiporo / Obayemi, John D / Oparah, Josephine C / Ezenwafor, Theresa C / Onwudiwe, Killian C / Ani, Chukwuemeka J / Biswas, Suchi S / Onyekanne, Chinyerem / Odusanya, Olushola S / Madukwe, Jonathan / Soboyejo, Winston O

    Journal of biomedical materials research. Part B, Applied biomaterials

    2022  Volume 111, Issue 3, Page(s) 665–683

    Abstract: This article presents silica nanoparticles for the sustained release of AMACR antibody-conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with ... ...

    Abstract This article presents silica nanoparticles for the sustained release of AMACR antibody-conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM-B), and capped with dextran (MCM-B-D). The nanoparticles were then characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X-ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α-Methyl Acyl-CoA racemase (AMACR) antibody-conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer-Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibody-conjugated DOX drug-loaded nanoparticles were more effective than the free DOX drug-loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug-eluting structures for the localized and targeted treatment of prostate cancer.
    MeSH term(s) Humans ; Male ; Delayed-Action Preparations/pharmacology ; Doxorubicin/pharmacology ; Doxorubicin/chemistry ; Nanoparticles/chemistry ; Prostatic Neoplasms/drug therapy ; Racemases and Epimerases/therapeutic use ; Silicon Dioxide/pharmacology ; Silicon Dioxide/chemistry
    Chemical Substances alpha-methylacyl-CoA racemase (EC 5.1.99.4) ; Delayed-Action Preparations ; Doxorubicin (80168379AG) ; Racemases and Epimerases (EC 5.1.-) ; Silicon Dioxide (7631-86-9)
    Language English
    Publishing date 2022-10-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2099992-6
    ISSN 1552-4981 ; 1552-4973 ; 0021-9304
    ISSN (online) 1552-4981
    ISSN 1552-4973 ; 0021-9304
    DOI 10.1002/jbm.b.35185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6196: Show issues Location:
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  6. Article ; Online: In vitro studies of Annona muricata L. extract-loaded electrospun scaffolds for localized treatment of breast cancer.

    Akpan, Udom M / Pellegrini, Michael / Salifu, Ali A / Obayemi, John D / Ezenwafor, Theresa / Browe, Daniel / Ani, Chukwuemeka J / Danyuo, Yiporo / Dozie-Nwachukwu, Stella / Odusanya, Olushola S / Freeman, Joseph / Soboyejo, Winston O

    Journal of biomedical materials research. Part B, Applied biomaterials

    2021  Volume 109, Issue 12, Page(s) 2041–2056

    Abstract: This paper presents in vitro studies of the sustained release of Annona muricata leaf extracts (AME) from hybrid electrospun fibers for breast cancer treatment. Electrospun hybrid scaffolds were fabricated from crude AME extracts, poly(lactic-co-glycolic ...

    Abstract This paper presents in vitro studies of the sustained release of Annona muricata leaf extracts (AME) from hybrid electrospun fibers for breast cancer treatment. Electrospun hybrid scaffolds were fabricated from crude AME extracts, poly(lactic-co-glycolic acid)/gelatin (PLGA/Ge) and pluronic F127. The physicochemical properties of the AME extract and scaffolds were studied. The antiproliferative effects of the scaffolds were also assessed on breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic breast (MCF10A) cell lines. Scanning electron microscope micrographs revealed a random network of micro- and submicron fibers. In vitro drug release profiles, governed by quasi-Fickian diffusion at pH 7.4 and non-Fickian super case II at pH 6.7, showed initial burst AME release from the PLGA/Ge-AME and PLGA/Ge-F127/AME fibers at pH 7.4, and burst release from PLGA/Ge-F127/AME (not observed from PLGA/Ge-AME) at pH 6.7. Then, a slower, sustained release of the remaining AME from the fibers, attributed to the onset of degradation of the PLGA/Ge backbone, was observed for the next 72 hr. The cumulative release of AME was 89.33 ± 0.73% (PLGA/Ge-AME) and 51.17 ± 7.96% (PLGA/Ge-F127/AME) at pH 7.4, and 9.27 ± 2.3% and 73.5 ± 4.5%, respectively, at pH 6.7. Pluronic F127 addition increased the drug loading capacity and prolonged the sustained AME release from the fibers. The released AME significantly inhibited the in vitro growth of the breast cancer cells more than the non-tumorigenic cells, due to the induction of apoptosis, providing evidence for using pluronic F127-containing electrospun fibers for sustained and localized AME delivery to breast cancer cells.
    MeSH term(s) Annona ; Breast Neoplasms/drug therapy ; Drug Liberation ; Female ; Humans ; Poloxamer/chemistry ; Poloxamer/pharmacology ; Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
    Chemical Substances Poloxamer (106392-12-5) ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS)
    Language English
    Publishing date 2021-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2099992-6
    ISSN 1552-4981 ; 1552-4973 ; 0021-9304
    ISSN (online) 1552-4981
    ISSN 1552-4973 ; 0021-9304
    DOI 10.1002/jbm.b.34852
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    Zs.A 6196: Show issues Location:
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