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290 results on '"Ljubimova, Julia Y."'

1. Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells

Author

Shah, Ruchi, Spektor, Tanya M., Weisenberger, Daniel J., Ding, Hui, Patil, Rameshwar, Amador, Cynthia, Song, Xue-Ying, Chun, Steven T., Inzalaco, Jake, Turjman, Sue, Ghiam, Sean, Jeong-Kim, Jiho, Tolstoff, Sasha, Yampolsky, Sabina V., Sawant, Onkar B., Rabinowitz, Yaron S., Maguen, Ezra, Hamrah, Pedram, Svendsen, Clive N., Saghizadeh, Mehrnoosh, Ljubimova, Julia Y., Kramerov, Andrei A., and Ljubimov, Alexander V.

Published
2023
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2. Novel nanopolymer RNA therapeutics normalize human diabetic corneal wound healing and epithelial stem cells

Author

Kramerov, Andrei A, Shah, Ruchi, Ding, Hui, Holler, Eggehard, Turjman, Sue, Rabinowitz, Yaron S, Ghiam, Sean, Maguen, Ezra, Svendsen, Clive N, Saghizadeh, Mehrnoosh, Ljubimova, Julia Y, and Ljubimov, Alexander V

Subjects
Biological Sciences, Chemical Sciences, Diabetes, Stem Cell Research - Nonembryonic - Human, Biotechnology, Regenerative Medicine, Genetics, Stem Cell Research, Eye Disease and Disorders of Vision, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, 2.1 Biological and endogenous factors, Aetiology, Eye, Adenoviridae, Adult, Aged, Aged, 80 and over, Biomarkers, Cell Survival, Cells, Cultured, Cornea, Diabetes Mellitus, Epithelial Cells, Female, Humans, Male, Middle Aged, Nanoparticles, Oligonucleotides, Antisense, Polymers, RNA, Receptors, Cell Surface, Signal Transduction, Stem Cells, Wound Healing, Diabetic cornea, Gene therapy, RNA therapeutics, miRNA, Nanobioconjugate, Wound healing, Limbal stem cells, Technology, Nanoscience & Nanotechnology, Biological sciences, Chemical sciences
Abstract

Human diabetic corneas develop delayed wound healing, epithelial stem cell dysfunction, recurrent erosions, and keratitis. Adenoviral gene therapy modulating c-Met, cathepsin F and MMP-10 normalized wound healing and epithelial stem cells in organ-cultured diabetic corneas but showed toxicity in stem cell-enriched cultured limbal epithelial cells (LECs). For a safer treatment, we engineered a novel nanobiopolymer (NBC) that carried antisense oligonucleotide (AON) RNA therapeutics suppressing cathepsin F or MMP-10, and miR-409-3p that inhibits c-Met. NBC was internalized by LECs through transferrin receptor (TfR)-mediated endocytosis, inhibited cathepsin F or MMP-10 and upregulated c-Met. Non-toxic NBC modulating c-Met and cathepsin F accelerated wound healing in diabetic LECs and organ-cultured corneas vs. control NBC. NBC treatment normalized levels of stem cell markers (keratins 15 and 17, ABCG2, and ΔNp63), and signaling mediators (p-EGFR, p-Akt and p-p38). Non-toxic nano RNA therapeutics thus present a safe alternative to viral gene therapy for normalizing diabetic corneal cells.

Published
2021

3. Multifunctional Nanopolymers for Blood–Brain Barrier Delivery and Inhibition of Glioblastoma Growth through EGFR/EGFRvIII, c-Myc, and PD-1

Author

Patil, Rameshwar, Sun, Tao, Rashid, Mohammad Harun, Israel, Liron L, Ramesh, Arshia, Davani, Saya, Black, Keith L, Ljubimov, Alexander V, Holler, Eggehard, and Ljubimova, Julia Y

Subjects
Engineering, Materials Engineering, Nanotechnology, Cancer, Brain Disorders, Biotechnology, Orphan Drug, Rare Diseases, Brain Cancer, Neurosciences, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Neurological, multifunctional drugs, blood-brain barrier, receptor-mediated transcytosis, brain tumor, delivery peptides, nanocarriers, cancer immunology, mRNA therapy, blood–brain barrier, Materials engineering
Abstract

Glioblastoma (GBM) is the most prevalent primary brain cancer in the pediatric and adult population. It is known as an untreatable tumor in urgent need of new therapeutic approaches. The objective of this work was to develop multifunctional nanomedicines to treat GBM in clinical practice using combination therapy for several targets. We developed multifunctional nanopolymers (MNPs) based on a naturally derived biopolymer, poly(β-L-malic) acid, which are suitable for central nervous system (CNS) treatment. These MNPs contain several anticancer functional moieties with the capacity of crossing the blood-brain barrier (BBB), targeting GBM cells and suppressing two important molecular markers, tyrosine kinase transmembrane receptors EGFR/EGFRvIII and c-Myc nuclear transcription factor. The reproducible syntheses of MNPs where monoclonal antibodies are replaced with AP-2 peptide for effective BBB delivery were presented. The active anticancer inhibitors of mRNA/protein syntheses were Morpholino antisense oligonucleotides (AONs). Two ways of covalent AON-polymer attachments with and without disulfide bonds were explored. These MNPs bearing AONs to EGFR/EGFRvIII and c-Myc, as well as in a combination with the polymer-attached checkpoint inhibitor anti-PD-1 antibody, orchestrated a multi-pronged attack on intracranial mouse GBM to successfully block tumor growth and significantly increase survival of brain tumor-bearing animals.

Published
2021

4. Exposure to environmental airborne particulate matter caused wide-ranged transcriptional changes and accelerated Alzheimer's-related pathology: A mouse study

Author

Israel, Liron L., Braubach, Oliver, Shatalova, Ekaterina S., Chepurna, Oksana, Sharma, Sachin, Klymyshyn, Dmytro, Galstyan, Anna, Chiechi, Antonella, Cox, Alysia, Herman, David, Bliss, Bishop, Hasen, Irene, Ting, Amanda, Arechavala, Rebecca, Kleinman, Michael T., Patil, Rameshwar, Holler, Eggehard, Ljubimova, Julia Y., Koronyo-Hamaoui, Maya, Sun, Tao, and Black, Keith L.

Published
2023
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6. Author Correction: Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy

Author

Galstyan, Anna, Markman, Janet L, Shatalova, Ekaterina S, Chiechi, Antonella, Korman, Alan J, Patil, Rameshwar, Klymyshyn, Dmytro, Tourtellotte, Warren G, Israel, Liron L, Braubach, Oliver, Ljubimov, Vladimir A, Mashouf, Leila A, Ramesh, Arshia, Grodzinski, Zachary B, Penichet, Manuel L, Black, Keith L, Holler, Eggehard, Sun, Tao, Ding, Hui, Ljubimov, Alexander V, and Ljubimova, Julia Y

Subjects
Biomedical and Clinical Sciences, Immunology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

7. Blockade of a laminin-411 - Notch axis with CRISPR/Cas9 or a nanobioconjugate inhibits glioblastoma growth through tumor-microenvironment crosstalk

Author

Sun, Tao, Patil, Rameshwar, Galstyan, Anna, Klymyshyn, Dmytro, Ding, Hui, Chesnokova, Alexandra, Cavenee, Webster K, Furnari, Frank B, Ljubimov, Vladimir A, Shatalova, Ekaterina S, Wagner, Shawn, Li, Debiao, Mamelak, Adam N, Bannykh, Serguei I, Patil, Chirag G, Rudnick, Jeremy D, Hu, Jethro, Grodzinski, Zachary B, Rekechenetskiy, Arthur, Falahatian, Vida, Lyubimov, Alexander V, Chen, Yongmei L, Leoh, Lai S, Daniels-Wells, Tracy R, Penichet, Manuel L, Holler, Eggehard, Ljubimov, Alexander V, Black, Keith L, and Ljubimova, Julia Y

Subjects
Brain Cancer, Cancer, Neurosciences, Rare Diseases, Brain Disorders, Stem Cell Research, Biotechnology, Stem Cell Research - Nonembryonic - Human, Animals, Apoptosis, Biomarkers, Tumor, Brain, CRISPR-Cas Systems, Cell Proliferation, Gene Expression Regulation, Neoplastic, Glioblastoma, Humans, Laminin, Mice, Mice, Nude, Nanoparticles, Neoplastic Stem Cells, Prognosis, Receptors, Notch, Signal Transduction, Survival Rate, Tumor Cells, Cultured, Tumor Microenvironment, Xenograft Model Antitumor Assays, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (α4β1γ1) with higher tumor grade and with expression of cancer stem cell (CSC) markers, including Notch pathway members, CD133, Nestin, and c-Myc. Laminin-411 overexpression also correlated with higher recurrence rate and shorter survival of GBM patients. We also showed that depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice and significantly increased survival of host animals compared with mice with untreated cells. Inhibition of laminin-411 suppressed Notch pathway in normal and malignant human brain cell types. A nanobioconjugate potentially suitable for clinical use and capable of crossing blood-brain barrier was designed to block laminin-411 expression. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, including the Notch axis. This study describes an efficient strategy for GBM treatment via targeting a critical component of the tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma.Significance: Laminin-411 expression in the glioma microenvironment correlates with Notch and other cancer stem cell markers and can be targeted by a novel, clinically translatable nanobioconjugate to inhibit glioma growth.

Published
2019

9. Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy

Author

Galstyan, Anna, Markman, Janet L, Shatalova, Ekaterina S, Chiechi, Antonella, Korman, Alan J, Patil, Rameshwar, Klymyshyn, Dmytro, Tourtellotte, Warren G, Israel, Liron L, Braubach, Oliver, Ljubimov, Vladimir A, Mashouf, Leila A, Ramesh, Arshia, Grodzinski, Zachary B, Penichet, Manuel L, Black, Keith L, Holler, Eggehard, Sun, Tao, Ding, Hui, Ljubimov, Alexander V, and Ljubimova, Julia Y

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Brain Disorders, Rare Diseases, Neurosciences, Biotechnology, Cancer, Brain Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Antineoplastic Agents, Immunological, Biopolymers, Blood-Brain Barrier, Brain Neoplasms, CTLA-4 Antigen, Cell Line, Tumor, Disease Models, Animal, Female, Glioma, Humans, Immunoconjugates, Malates, Mice, Nanoconjugates, Permeability, Physarum polycephalum, Polymers, Programmed Cell Death 1 Receptor, Treatment Outcome
Abstract

Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their inability to cross blood-brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB and activation of local brain anti-tumor immune response. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of tumor-targeted polymer-conjugated checkpoint inhibitors as an effective GBM treatment via activation of both systemic and local privileged brain tumor immune response.

Published
2019

10. Coarse particulate matter (PM2.5-10) in Los Angeles Basin air induces expression of inflammation and cancer biomarkers in rat brains.

Author

Ljubimova, Julia Y, Braubach, Oliver, Patil, Rameshwar, Chiechi, Antonella, Tang, Jie, Galstyan, Anna, Shatalova, Ekaterina S, Kleinman, Michael T, Black, Keith L, and Holler, Eggehard

Subjects
Animals, Rats, Encephalitis, Brain Neoplasms, Nickel, Air Pollutants, Spectrophotometry, Atomic, Gene Expression Profiling, Sequence Analysis, RNA, Organ Specificity, Gene Expression Regulation, Brain Chemistry, Particle Size, Time Factors, Los Angeles, Particulate Matter, Biomarkers, Tumor
Abstract

Air pollution is linked to brain inflammation, which accelerates tumorigenesis and neurodegeneration. The molecular mechanisms that connect air pollution with brain pathology are largely unknown but seem to depend on the chemical composition of airborne particulate matter (PM). We sourced ambient PM from Riverside, California, and selectively exposed rats to coarse (PM2.5-10: 2.5-10 µm), fine (PM

Published
2018

12. Covalent nano delivery systems for selective imaging and treatment of brain tumors.

Author

Ljubimova, Julia Y, Sun, Tao, Mashouf, Leila, Ljubimov, Alexander V, Israel, Liron L, Ljubimov, Vladimir A, Falahatian, Vida, and Holler, Eggehard

Subjects
Blood-Brain Barrier, Animals, Humans, Brain Neoplasms, Antineoplastic Agents, Drug Delivery Systems, Nanomedicine, Molecular Imaging, Nanoconjugates, Blood-brain-barrier, Brain cancer, Covalent nano conjugates, Drug delivery, Nanomedicine for brain imaging, Biomedical Imaging, Bioengineering, Brain Disorders, Nanotechnology, Brain Cancer, Biotechnology, Cancer, Orphan Drug, Neurosciences, Rare Diseases, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Neurological, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy
Abstract

Nanomedicine is a rapidly evolving form of therapy that holds a great promise for superior drug delivery efficiency and therapeutic efficacy than conventional cancer treatment. In this review, we attempt to cover the benefits and the limitations of current nanomedicines with special attention to covalent nano conjugates for imaging and drug delivery in the brain. The improvement in brain tumor treatment remains dismal despite decades of efforts in drug development and patient care. One of the major obstacles in brain cancer treatment is the poor drug delivery efficiency owing to the unique blood-brain barrier (BBB) in the CNS. Although various anti-cancer agents are available to treat tumors outside of the CNS, the majority fails to cross the BBB. In this regard, nanomedicines have increasingly drawn attention due to their multi-functionality and versatility. Nano drugs can penetrate BBB and other biological barriers, and selectively accumulate in tumor cells, while concurrently decreasing systemic toxicity.

Published
2017

16. Simultaneous blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme

Author

Chou, Szu-Ting, Patil, Rameshwar, Galstyan, Anna, Gangalum, Pallavi R, Cavenee, Webster K, Furnari, Frank B, Ljubimov, Vladimir A, Chesnokova, Alexandra, Kramerov, Andrei A, Ding, Hui, Falahatian, Vida, Mashouf, Leila, Fox, Irving, Black, Keith L, Holler, Eggehard, Ljubimov, Alexander V, and Ljubimova, Julia Y

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Bioengineering, Neurosciences, Rare Diseases, Brain Disorders, Cancer, Brain Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Adult, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Blood-Brain Barrier, Brain Neoplasms, Casein Kinase II, Cell Line, Tumor, ErbB Receptors, Female, Glioblastoma, Humans, Malates, Mice, Mice, Nude, Nanoconjugates, Neoplastic Stem Cells, Oligonucleotides, Antisense, Polyethylene Glycols, Polymers, Signal Transduction, Surface Properties, Glioblastoma multiforme, Dual antisense oligonucleotide-dual antibody nanobioconjugate, Blood-brain barrier delivery, Protein kinase CK2, EGFR/EGFRvIII, Biomedical Engineering, Chemical Engineering, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences, Biomedical engineering
Abstract

Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults. GBM tumors are also notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database. Two xenogeneic mouse models bearing intracranial human GBMs from cell lines LN229 and U87MG that expressed both CK2 and EGFR at different levels were used. Simultaneous knockdown of CK2α and EGFR/EGFRvIII suppressed their downstream prosurvival signaling. Treatment also markedly reduced the expression of programmed death-ligand 1 (PD-L1), a negative regulator of cytotoxic lymphocytes. Downregulation of CK2 and EGFR also caused deactivation of heat shock protein 90 (Hsp90) co-chaperone Cdc37, which may suppress the activity of key cellular kinases. Inhibition of either target was associated with downregulation of the other target as well, which may underlie the increased efficacy of the dual nanobioconjugate that is directed against both CK2 and EGFR. Importantly, the single nanodrugs, and especially the dual nanodrug, markedly suppressed the expression of the cancer stem cell markers c-Myc, CD133, and nestin, which could contribute to the efficacy of the treatments. In both tumor models, the nanobioconjugates significantly increased (up to 2-fold) animal survival compared with the PBS-treated control group. The versatile nanobioconjugates developed in this study, with the abilities of anti-cancer drug delivery across biobarriers and the inhibition of key tumor regulators, offer a promising nanotherapeutic approach to treat GBMs, and to potentially prevent drug resistance and retard the recurrence of brain tumors.

Published
2016

20. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Author

Anjum, Samreen, Arachchi, Harindra, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnett, Gene, Baylin, Stephen, Bell, Sue, Benz, Christopher, Bir, Natalie, Black, Keith L., Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bowen, Jay, Bristow, Christopher A., Butterfield, Yaron S.N., Chen, Qing-Rong, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Coetzee, Simon G., Cohen, Mark L., Colman, Howard, Couce, Marta, D’Angelo, Fulvio, Davidsen, Tanja, Davis, Amy, Demchok, John A., Devine, Karen, Ding, Li, Duell, Rebecca, Elder, J. Bradley, Eschbacher, Jennifer M., Fehrenbach, Ashley, Ferguson, Martin, Frazer, Scott, Fuller, Gregory, Fulop, Jordonna, Gabriel, Stacey B., Garofano, Luciano, Gastier-Foster, Julie M., Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Giannini, Caterina, Gibson, William J., Hadjipanayis, Angela, Hayes, D. Neil, Heiman, David I., Hermes, Beth, Hilty, Joe, Hoadley, Katherine A., Hoyle, Alan P., Huang, Mei, Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J.M., Ju, Zhenlin, Kastl, Alison, Kendler, Ady, Kim, Jaegil, Kucherlapati, Raju, Lai, Phillip H., Lawrence, Michael S., Lee, Semin, Leraas, Kristen M., Lichtenberg, Tara M., Lin, Pei, Liu, Yuexin, Liu, Jia, Ljubimova, Julia Y., Lu, Yiling, Ma, Yussanne, Maglinte, Dennis T., Mahadeshwar, Harshad S., Marra, Marco A., McGraw, Mary, McPherson, Christopher, Meng, Shaowu, Mieczkowski, Piotr A., Miller, C. Ryan, Mills, Gordon B., Moore, Richard A., Mose, Lisle E., Mungall, Andrew J., Naresh, Rashi, Naska, Theresa, Neder, Luciano, Noble, Michael S., Noss, Ardene, O’Neill, Brian Patrick, Ostrom, Quinn T., Palmer, Cheryl, Pantazi, Angeliki, Parfenov, Michael, Park, Peter J., Parker, Joel S., Perou, Charles M., Pierson, Christopher R., Pihl, Todd, Protopopov, Alexei, Radenbaugh, Amie, Ramirez, Nilsa C., Rathmell, W. Kimryn, Ren, Xiaojia, Roach, Jeffrey, Robertson, A. Gordon, Saksena, Gordon, Schein, Jacqueline E., Schumacher, Steven E., Seidman, Jonathan, Senecal, Kelly, Seth, Sahil, Shen, Hui, Shi, Yan, Shih, Juliann, Shimmel, Kristen, Sicotte, Hugues, Sifri, Suzanne, Silva, Tiago, Simons, Janae V., Singh, Rosy, Skelly, Tara, Sloan, Andrew E., Sofia, Heidi J., Soloway, Matthew G., Song, Xingzhi, Sougnez, Carrie, Souza, Camila, Staugaitis, Susan M., Sun, Huandong, Sun, Charlie, Tan, Donghui, Tang, Jiabin, Tang, Yufang, Thorne, Leigh, Trevisan, Felipe Amstalden, Triche, Timothy, Van Den Berg, David J., Veluvolu, Umadevi, Voet, Doug, Wan, Yunhu, Wang, Zhining, Warnick, Ronald, Weinstein, John N., Weisenberger, Daniel J., Wilkerson, Matthew D., Williams, Felicia, Wise, Lisa, Wolinsky, Yingli, Wu, Junyuan, Xu, Andrew W., Yang, Lixing, Yang, Liming, Zack, Travis I., Zenklusen, Jean C., Zhang, Jianhua, Zhang, Wei, Zhang, Jiashan, Zmuda, Erik, Ceccarelli, Michele, Barthel, Floris P., Malta, Tathiane M., Sabedot, Thais S., Salama, Sofie R., Murray, Bradley A., Morozova, Olena, Newton, Yulia, Pagnotta, Stefano M., Wang, Jiguang, Manyam, Ganiraju, Zoppoli, Pietro, Ling, Shiyun, Rao, Arjun A., Grifford, Mia, Cherniack, Andrew D., Zhang, Hailei, Poisson, Laila, Carlotti, Carlos Gilberto, Jr., Tirapelli, Daniela Pretti da Cunha, Rao, Arvind, Mikkelsen, Tom, Lau, Ching C., Yung, W.K. Alfred, Rabadan, Raul, Huse, Jason, Brat, Daniel J., Lehman, Norman L., Barnholtz-Sloan, Jill S., Zheng, Siyuan, Hess, Kenneth, Rao, Ganesh, Meyerson, Matthew, Beroukhim, Rameen, Cooper, Lee, Akbani, Rehan, Wrensch, Margaret, Haussler, David, Aldape, Kenneth D., Laird, Peter W., Gutmann, David H., Noushmehr, Houtan, Iavarone, Antonio, and Verhaak, Roel G.W.

Published
2016
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22. Supplementary Data 5 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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23. Data from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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24. Supplementary Data 8 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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25. Supplementary Data 6 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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26. Supplementary Video from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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27. Supplementary Data 2 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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28. Supplementary Data 7 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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29. Supplementary Data 3 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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30. Supplementary Data 4 from Blockade of a Laminin-411–Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk

Author

Sun, Tao, primary, Patil, Rameshwar, primary, Galstyan, Anna, primary, Klymyshyn, Dmytro, primary, Ding, Hui, primary, Chesnokova, Alexandra, primary, Cavenee, Webster K., primary, Furnari, Frank B., primary, Ljubimov, Vladimir A., primary, Shatalova, Ekaterina S., primary, Wagner, Shawn, primary, Li, Debiao, primary, Mamelak, Adam N., primary, Bannykh, Serguei I., primary, Patil, Chirag G., primary, Rudnick, Jeremy D., primary, Hu, Jethro, primary, Grodzinski, Zachary B., primary, Rekechenetskiy, Arthur, primary, Falahatian, Vida, primary, Lyubimov, Alexander V., primary, Chen, Yongmei L., primary, Leoh, Lai S., primary, Daniels-Wells, Tracy R., primary, Penichet, Manuel L., primary, Holler, Eggehard, primary, Ljubimov, Alexander V., primary, Black, Keith L., primary, and Ljubimova, Julia Y., primary

Published
2023
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32. Signature Effects of Vector-Guided Systemic Nano Bioconjugate Delivery Across Blood-Brain Barrier of Normal, Alzheimer’s, and Tumor Mouse Models

Author

Israel, Liron L., primary, Galstyan, Anna, additional, Cox, Alysia, additional, Shatalova, Ekaterina S., additional, Sun, Tao, additional, Rashid, Mohammad-Harun, additional, Grodzinski, Zachary, additional, Chiechi, Antonella, additional, Fuchs, Dieu-Trang, additional, Patil, Rameshwar, additional, Koronyo-Hamaoui, Maya, additional, Black, Keith L., additional, Ljubimova, Julia Y., additional, and Holler, Eggehard, additional

Published
2022
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36. The Somatic Genomic Landscape of Glioblastoma

Author

Benz, Christopher, Barnholtz-Sloan, Jill, Barrett, Wendi, Ostrom, Quinn, Wolinsky, Yingli, Black, Keith L., Bose, Bikash, Boulos, Paul T., Boulos, Madgy, Brown, Jenn, Czerinski, Christine, Eppley, Matthew, Iacocca, Mary, Kempista, Thelma, Kitko, Teresa, Koyfman, Yakov, Rabeno, Brenda, Rastogi, Pawan, Sugarman, Michael, Swanson, Patricia, Yalamanchii, Kennedy, Otey, Ilana P., Liu, Yingchun Spring, Xiao, Yonghong, Auman, J.Todd, Chen, Peng-Chieh, Hadjipanayis, Angela, Lee, Eunjung, Lee, Semin, Park, Peter J., Seidman, Jonathan, Yang, Lixing, Kucherlapati, Raju, Kalkanis, Steven, Mikkelsen, Tom, Poisson, Laila M., Raghunathan, Aditya, Scarpace, Lisa, Bernard, Brady, Bressler, Ryan, Eakin, Andrea, Iype, Lisa, Kreisberg, Richard B., Leinonen, Kalle, Reynolds, Sheila, Rovira, Hector, Thorsson, Vesteinn, Shmulevich, Ilya, Annala, Matti J., Penny, Robert, Paulauskis, Joseph, Curley, Erin, Hatfield, Martha, Mallery, David, Morris, Scott, Shelton, Troy, Shelton, Candace, Sherman, Mark, Yena, Peggy, Cuppini, Lucia, DiMeco, Francesco, Eoli, Marica, Finocchiaro, Gaetano, Maderna, Emanuela, Pollo, Bianca, Saini, Marco, Balu, Saianand, Hoadley, Katherine A., Li, Ling, Miller, C. Ryan, Shi, Yan, Topal, Michael D., Wu, Junyuan, Dunn, Gavin, Giannini, Caterina, O'Neill, Brian P., Aksoy, B. Arman, Antipin, Yevgeniy, Borsu, Laetitia, Berman, Samuel H., Brennan, Cameron W., Cerami, Ethan, Chakravarty, Debyani, Ciriello, Giovanni, Gao, Jianjiong, Gross, Benjamin, Jacobsen, Anders, Ladanyi, Marc, Lash, Alex, Liang, Yupu, Reva, Boris, Sander, Chris, Schultz, Nikolaus, Shen, Ronglai, Socci, Nicholas D., Viale, Agnes, Ferguson, Martin L., Chen, Qing-Rong, Demchok, John A., Dillon, Laura A.L., Shaw, Kenna R. Mills, Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Davidsen, Tanja, Guyer, Mark S., Ozenberger, Bradley A., Sofia, Heidi J., Bergsten, Julie, Eckman, John, Harr, Jodi, Myers, Jerome, Smith, Christine, Tucker, Kelly, Winemiller, Cindy, Zach, Leigh Anne, Ljubimova, Julia Y., Eley, Greg, Ayala, Brenda, Jensen, Mark A., Kahn, Ari, Pihl, Todd D., Pot, David A., Wan, Yunhu, Eschbacher, Jennifer, Foltz, Greg, Hansen, Nathan, Hothi, Parvi, Lin, Biaoyang, Shah, Nameeta, Yoon, Jae-geun, Lau, Ching, Berens, Michael, Ardlie, Kristin, Beroukhim, Rameen, Carter, Scott L., Cherniack, Andrew D., Noble, Mike, Cho, Juok, Cibulskis, Kristian, DiCara, Daniel, Frazer, Scott, Gabriel, Stacey B., Gehlenborg, Nils, Gentry, Jeff, Heiman, David, Kim, Jaegil, Jing, Rui, Lander, Eric S., Lawrence, Michael, Lin, Pei, Mallard, Will, Meyerson, Matthew, Onofrio, Robert C., Saksena, Gordon, Schumacher, Steve, Sougnez, Carrie, Stojanov, Petar, Tabak, Barbara, Voet, Doug, Zhang, Hailei, Zou, Lihua, Getz, Gad, Dees, Nathan N., Ding, Li, Fulton, Lucinda L., Fulton, Robert S., Kanchi, Krishna-Latha, Mardis, Elaine R., Wilson, Richard K., Baylin, Stephen B., Andrews, David W., Harshyne, Larry, Cohen, Mark L., Devine, Karen, Sloan, Andrew E., VandenBerg, Scott R., Berger, Mitchel S., Prados, Michael, Carlin, Daniel, Craft, Brian, Ellrott, Kyle, Goldman, Mary, Goldstein, Theodore, Grifford, Mia, Haussler, David, Ma, Singer, Ng, Sam, Salama, Sofie R., Sanborn, J. Zachary, Stuart, Joshua, Swatloski, Teresa, Waltman, Peter, Zhu, Jing, Foss, Robin, Frentzen, Barbara, Friedman, William, McTiernan, Raquel, Yachnis, Anthony, Hayes, D. Neil, Perou, Charles M., Zheng, Siyuan, Vegesna, Rahulsimham, Mao, Yong, Akbani, Rehan, Aldape, Kenneth, Bogler, Oliver, Fuller, Gregory N., Liu, Wenbin, Liu, Yuexin, Lu, Yiling, Mills, Gordon, Protopopov, Alexei, Ren, Xiaojia, Sun, Youting, Wu, Chang-Jiun, Yung, W.K. Alfred, Zhang, Wei, Zhang, Jianhua, Chen, Ken, Weinstein, John N., Chin, Lynda, Verhaak, Roel G.W., Noushmehr, Houtan, Weisenberger, Daniel J., Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy J., Jr., Van Den Berg, David J., Laird, Peter W., Gutmann, David H., Lehman, Norman L., VanMeir, Erwin G., Brat, Daniel, Olson, Jeffrey J., Mastrogianakis, Gena M., Devi, Narra S., Zhang, Zhaobin, Bigner, Darell, Lipp, Eric, McLendon, Roger, McKenna, Aaron, Campos, Benito, Genovese, Giannicola, Shukla, Sachet A., Yung, W.K., Bigner, Darell D., Van Meir, Erwin G., Sloan, Andrew, Guha, Abhijit, O’Neill, Brian P., Gibbs, Richard, Marra, Marco, Mills, Gordon B., Lander, Eric, Spellman, Paul, Wilson, Richard, Weinstein, John, and Gabriel, Stacey

Published
2013
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39. Single- and Multi-Arm Gadolinium MRI Contrast Agents for Targeted Imaging of Glioblastoma

Author

Patil, Rameshwar, Galstyan, Anna, Grodzinski, Zachary B, Shatalova, Ekaterina S, Wagner, Shawn, Israel, Liron L, Ding, Hui, Black, Keith L, Ljubimova, Julia Y, and Holler, Eggehard

Subjects
tumor targeting, Brain Neoplasms, accelerated diagnosis, Contrast Media, Mice, Nude, blood–brain barrier, structure variation, Magnetic Resonance Imaging, Xenograft Model Antitumor Assays, Nanostructures, Disease Models, Animal, Meglumine, International Journal of Nanomedicine, Gd-DOTA, Heterocyclic Compounds, Cell Line, Tumor, Organometallic Compounds, Animals, Humans, Female, Glioblastoma, Original Research
Abstract

Rameshwar Patil,1 Anna Galstyan,1 Zachary B Grodzinski,1 Ekaterina S Shatalova,1 Shawn Wagner,2 Liron L Israel,1 Hui Ding,1 Keith L Black,1 Julia Y Ljubimova,1,3 Eggehard Holler1 1Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Oncology Translational Program, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USACorrespondence: Eggehard HollerNanomedicine Research Center, Department of Neurosurgery, Cedars Sinai Medical Center, 127 S. San Vicente Boulevard, Suite A8304, Los Angeles, CA 90048 Tel +1 310 423-6630Email eggehard.holler@cshs.orgBackground: Position of gadolinium atom(s) plays a key role in contrast enhancement of gadolinium-based contrast agents. To gain a better understanding of effects of distance of gadolinium in relation to the nanoconjugate platform, we designed and synthesized single- and multi-arm (“star”) gadolinium conjugates equipped with antibody and peptides for targeting. The contrast agents were studied for their tumor imaging performance in a glioma mouse model.Materials and Methods: Antibody- and peptide-targeted nano contrast agents (NCAs) were synthesized using polymalic acid platforms of different sizes. Gadolinium-DOTA and intermediates were attached as amides and targeting agents such as antibodies and peptides as thioethers. For in vivo experiments, we used human U87MG xenografts as glioma models. Magnetic resonance imaging (MRI)was performed on a Bruker BioSpec 94/20USR 9.4 T small-animal scanner. Delivery of contrast agents across theblood–brain barrier was studied by fluorescent microscopy.Results: All contrast agents accumulated into tumor and showed composition-dependent imaging performance. Peptide-targeted mini-NCAs had hydrodynamic diameters in the range 5.2– 9.4 nm and antibody-targeted NCAs haddiameters in the range 15.8– 20.5 nm. Zeta potentials were in the range of – 5.4–− 8.2 mV and − 4.6–− 8.8 mV, respectively. NCAs showed superior relaxivities compared to MultiHance at 9.4 T. The signal enhancement indicated maximum accumulation in tumor 30– 60 minutes after intravenous injection of the mouse tail vein. Only targeted NCAs wereretained in tumor for up to 3 hours and displayed contrast enhancement.Conclusion: The novel targeted NCAs with star-PEG features displayed improved relaxivity and greater contrast compared with commercial MultiHance contrast agent. The enhancement by mini-NCAs showed clearance of tumor contrast after 3 hours providing a suitable time window for tumor diagnosis in clinics. The technology provides a great tool with the promise of differential MRI diagnosis of brain tumors.Keywords: magnetic resonance imaging, Gd-DOTA, structure variation, blood–brain barrier, tumor targeting, accelerated diagnosis

Published
2020

41. Applying lessons learned from nanomedicines to understand rare hypersensitivity reactions to mRNA-based SARS-CoV-2 vaccines

Author

Afd Pharmaceutics, Pharmaceutics, Szebeni, Janos, Storm, Gert, Ljubimova, Julia Y., Castells, Mariana, Phillips, Elizabeth J., Turjeman, Keren, Barenholz, Yechezkel, Crommelin, Daan J.A., Dobrovolskaia, Marina A., Afd Pharmaceutics, Pharmaceutics, Szebeni, Janos, Storm, Gert, Ljubimova, Julia Y., Castells, Mariana, Phillips, Elizabeth J., Turjeman, Keren, Barenholz, Yechezkel, Crommelin, Daan J.A., and Dobrovolskaia, Marina A.

Published
2022

42. Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: What should be the policy?

Author

Kateb, Babak, Chiu, Katherine, Black, Keith L., Yamamoto, Vicky, Khalsa, Bhavraj, Ljubimova, Julia Y., Ding, Hui, Patil, Rameshwar, Portilla-Arias, Jose Antonio, Modo, Mike, Moore, David F., Farahani, Keyvan, Okun, Michael S., Prakash, Neal, Neman, Josh, Ahdoot, Daniel, Grundfest, Warren, Nikzad, Shouleh, and Heiss, John D.

Published
2011
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47. Inhibition of brain tumor growth by intravenous poly ([beta]-L-malic acid) nanobioconjugate with pH-dependent drug release

Author

Ding, Hui, Inoue, Satoshi, Ljubimov, Alexander V., Patil, Rameshwar, Portilla-Arias, Jose, Hu, Jinwei, Konda, Bindu, Wawrowsky, Kolja A., Fujita, Manabu, Karabalin, Natalya, Sasaki, Takako, Black, Keith L., Holler, Eggehard, and Ljubimova, Julia Y.

Subjects
Brain tumors -- Care and treatment, Malic acid -- Dosage and administration, Drug delivery systems -- Research, Drugs -- Vehicles, Drugs -- Research, Science and technology
Abstract

Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood--brain barrier (BBB) or blood--brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v. treatment of brain tumors. The polymeric drug passes through the BTB and tumor cell membrane using tandem monoclonal antibodies targeting the BTB and tumor cells. The next step for polymeric drug action was inhibition of tumor angiogenesis by specifically blocking the synthesis of a tumor neovascular trimer protein, laminin-411, by attached anti-sense oligonucleotides (AONs). The AONs were released into the target cell cytoplasm via pH-activated trileucine, an endosomal escape moiety. Drug delivery to the brain tumor and the release mechanism were both studied for this nanobiopolymer. Introduction of a trileucine endosome escape unit resulted in significantly increased AON delivery to tumor cells, inhibition of laminin-411 synthesis in vitro and in vivo, specific accumulation in brain tumors, and suppression of intracranial glioma growth compared with pH-independent leucine ester. The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy of glioma treatment. This delivery system with drug release into the brain-specific cell type could be useful for treatment of various brain pathologies. glioma treatment | polymalic acid | laminin-411 | endosomal escape | blood-brain barrier doi/ 10.1073/pnas.1003919107

Published
2010

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