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  1. Article ; Online: RNA delivery systems.

    Bhatia, Sangeeta N / Dahlman, James E

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 11, Page(s) e2315789121

    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2315789121
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
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  2. Article ; Online: Virtual Undergraduate Research Experiences: More Than a Pandemic Stopgap.

    Samad, Tahoura / Fleming, Heather E / Bhatia, Sangeeta N

    Med (New York, N.Y.)

    2022  Volume 2, Issue 2, Page(s) 118–121

    Abstract: During the SARS-CoV-2 pandemic, experimental research groups face a unique challenge: how to train undergraduates without access to labs. We share our experience developing entirely virtual undergraduate research internships and make a case for virtual ... ...

    Abstract During the SARS-CoV-2 pandemic, experimental research groups face a unique challenge: how to train undergraduates without access to labs. We share our experience developing entirely virtual undergraduate research internships and make a case for virtual research as a complement to traditional undergraduate mentoring, even after the resolution of the pandemic.
    MeSH term(s) COVID-19/epidemiology ; Humans ; Mentoring ; Pandemics ; SARS-CoV-2 ; Students
    Language English
    Publishing date 2022-02-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2021.01.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics.

    Buss, Colin G / Bhatia, Sangeeta N

    Proceedings of the National Academy of Sciences of the United States of America

    2020  Volume 117, Issue 24, Page(s) 13428–13436

    Abstract: The recent advent of immune checkpoint inhibitor (CPI) antibodies has revolutionized many aspects of cancer therapy, but the efficacy of these breakthrough therapeutics remains limited, as many patients fail to respond for reasons that still largely ... ...

    Abstract The recent advent of immune checkpoint inhibitor (CPI) antibodies has revolutionized many aspects of cancer therapy, but the efficacy of these breakthrough therapeutics remains limited, as many patients fail to respond for reasons that still largely evade understanding. An array of studies in human patients and animal models has demonstrated that local signaling can generate strongly immunosuppressive microenvironments within tumors, and emerging evidence suggests that delivery of immunostimulatory molecules into tumors can have therapeutic effects. Nanoparticle formulations of these cargoes offer a promising way to maximize their delivery and to enhance the efficacy of checkpoint inhibitors. We developed a modular nanoparticle system capable of encapsulating an array of immunostimulatory oligonucleotides that, in some cases, greatly increase their potency to activate inflammatory signaling within immune cells in vitro. We hypothesized that these immunostimulatory nanoparticles could suppress tumor growth by activating similar signaling in vivo, and thereby also improve responsiveness to immune checkpoint inhibitor antibody therapies. We found that our engineered nanoparticles carrying a CpG DNA ligand of TLR9 can suppress tumor growth in several animal models of various cancers, resulting in an abscopal effect on distant tumors, and improving responsiveness to anti-CTLA4 treatment with combinatorial effects after intratumoral administration. Moreover, by incorporating tumor-homing peptides, immunostimulatory nucleotide-bearing nanoparticles facilitate antitumor efficacy after systemic intravenous (i.v.) administration.
    MeSH term(s) Adjuvants, Immunologic ; Animals ; Antineoplastic Agents, Immunological/therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors ; Cell Line ; Drug Delivery Systems ; Drug Therapy, Combination ; Immunotherapy/methods ; Inflammation ; Macrophages/drug effects ; Macrophages/immunology ; Mice ; Nanoparticles/chemistry ; Neoplasms, Experimental/therapy ; Oligonucleotides/chemistry ; Oligonucleotides/immunology ; Oligonucleotides/therapeutic use
    Chemical Substances Adjuvants, Immunologic ; Antineoplastic Agents, Immunological ; CTLA-4 Antigen ; Ctla4 protein, mouse ; Oligonucleotides
    Language English
    Publishing date 2020-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2001569117
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    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  4. Article ; Online: Activity-Based Diagnostics: An Emerging Paradigm for Disease Detection and Monitoring.

    Soleimany, Ava P / Bhatia, Sangeeta N

    Trends in molecular medicine

    2020  Volume 26, Issue 5, Page(s) 450–468

    Abstract: Diagnostics to accurately detect disease and monitor therapeutic response are essential for effective clinical management. Bioengineering, chemical biology, molecular biology, and computer science tools are converging to guide the design of diagnostics ... ...

    Abstract Diagnostics to accurately detect disease and monitor therapeutic response are essential for effective clinical management. Bioengineering, chemical biology, molecular biology, and computer science tools are converging to guide the design of diagnostics that leverage enzymatic activity to measure or produce biomarkers of disease. We review recent advances in the development of these 'activity-based diagnostics' (ABDx) and their application in infectious and noncommunicable diseases. We highlight efforts towards both molecular probes that respond to disease-specific catalytic activity to produce a diagnostic readout, as well as diagnostics that use enzymes as an engineered component of their sense-and-respond cascade. These technologies exemplify how integrating techniques from multiple disciplines with preclinical validation has enabled ABDx that may realize the goals of precision medicine.
    MeSH term(s) Animals ; Biomarkers/metabolism ; Drug Monitoring/methods ; Humans ; Infections/diagnosis ; Infections/metabolism ; Noncommunicable Diseases/prevention & control ; Precision Medicine/methods
    Chemical Substances Biomarkers
    Language English
    Publishing date 2020-04-05
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2036490-8
    ISSN 1471-499X ; 1471-4914
    ISSN (online) 1471-499X
    ISSN 1471-4914
    DOI 10.1016/j.molmed.2020.01.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4345: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Conditional Antimicrobial Peptide Therapeutics.

    Ngambenjawong, Chayanon / Chan, Leslie W / Fleming, Heather E / Bhatia, Sangeeta N

    ACS nano

    2022  Volume 16, Issue 10, Page(s) 15779–15791

    Abstract: Antimicrobial peptides (AMPs) constitute a promising class of alternatives to antibiotics to curb antimicrobial resistance. Nonetheless, their utility as a systemic agent is hampered by short circulation time and toxicity. Infection sites, analogous to ... ...

    Abstract Antimicrobial peptides (AMPs) constitute a promising class of alternatives to antibiotics to curb antimicrobial resistance. Nonetheless, their utility as a systemic agent is hampered by short circulation time and toxicity. Infection sites, analogous to tumors, harbor an aberrant microenvironment that has the potential to be exploited to develop conditionally activated therapeutics with an improved therapeutic index. In particular, we identified strategies to prolong systemic circulation of small, cationic AMPs in a mouse model of bacterial pneumonia. Specifically, we report an albumin-binding domain (ABD)-AMP conjugate as a long-circulating conditional AMP therapeutic with a masked activity that can be liberated by proteases in the infected tissue microenvironment. Our systemically administered conjugate enhanced the pulmonary delivery of active AMP while also reducing AMP exposure to other off-target organs. Importantly, this reduction in off-target exposure improved the safety profile of the AMP. The framework we present can be generalized to quantify and optimize the performance of this emerging class of conditional therapeutics.
    MeSH term(s) Animals ; Mice ; Albumins ; Anti-Bacterial Agents ; Antimicrobial Peptides/therapeutic use ; Peptide Hydrolases
    Chemical Substances Albumins ; Anti-Bacterial Agents ; Antimicrobial Peptides ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2022-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1936-086X
    ISSN (online) 1936-086X
    DOI 10.1021/acsnano.2c04162
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Cancer nanomedicine.

    Bhatia, Sangeeta N / Chen, Xiaoyuan / Dobrovolskaia, Marina A / Lammers, Twan

    Nature reviews. Cancer

    2022  Volume 22, Issue 10, Page(s) 550–556

    MeSH term(s) Humans ; Nanomedicine ; Neoplasms/genetics ; Neoplasms/therapy
    Language English
    Publishing date 2022-08-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2062767-1
    ISSN 1474-1768 ; 1474-175X
    ISSN (online) 1474-1768
    ISSN 1474-175X
    DOI 10.1038/s41568-022-00496-9
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5563: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Zs.MG 24: Show issues

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  7. Article ; Online: Peptide Spiders: Peptide-Polymer Conjugates to Traffic Nucleic Acids.

    Kwon, Ester J / Ko, Henry / Bhatia, Sangeeta N

    Molecular pharmaceutics

    2020  Volume 17, Issue 9, Page(s) 3633–3642

    Abstract: Therapeutic nucleic acids hold great promise for the treatment of genetic diseases, yet the delivery of this highly charged macromolecular drug remains a challenge in the field. Peptides are promising agents to mediate nucleic acid delivery because they ... ...

    Abstract Therapeutic nucleic acids hold great promise for the treatment of genetic diseases, yet the delivery of this highly charged macromolecular drug remains a challenge in the field. Peptides are promising agents to mediate nucleic acid delivery because they can encode a biological function to overcome the trafficking barriers. Electrostatic nanocomplexes of nucleic acid and peptides can achieve effective delivery, but the balance between their stability and biological function must be finely tuned. In this work, we explore two peptide building blocks that have been studied in the literature: targeting ligands and intracellular trafficking peptides. We grafted these peptides on a polyethylene glycol (PEG) backbone with eight sites for substitution to create so-called "peptide spiders". These conjugates achieve stability via the well-known hydrophilic shielding effect of PEG. In addition, the coordination of peptide building blocks into multimers may create new biological properties, such as the well-known phenomena of increased binding avidity with multivalent ligands. In this work, we linked two trafficking peptides to the PEG backbone using either nonreducible or reducible chemistries and investigated the ability of these materials to carry silencing RNAs into mammalian cells. We then investigated these nanomaterials for their pharmacokinetic properties and silencing of undruggable targets in a mouse model of cancer. While reducible linkages were more potent at silencing in vitro, this effect was reversed when applied in the context of living animals. This work offers an insight into peptide-based delivery materials and investigates peptide-polymer linkages.
    MeSH term(s) Animals ; Cell Line, Tumor ; Female ; Humans ; Ligands ; Macromolecular Substances/chemistry ; Mice ; Mice, Nude ; Nanoparticles/chemistry ; Neoplasms/metabolism ; Nucleic Acids/chemistry ; Peptides/chemistry ; Polyethylene Glycols/chemistry ; Polymers/chemistry ; RNA, Small Interfering/chemistry ; U937 Cells
    Chemical Substances Ligands ; Macromolecular Substances ; Nucleic Acids ; Peptides ; Polymers ; RNA, Small Interfering ; Polyethylene Glycols (3WJQ0SDW1A)
    Language English
    Publishing date 2020-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2138405-8
    ISSN 1543-8392 ; 1543-8384
    ISSN (online) 1543-8392
    ISSN 1543-8384
    DOI 10.1021/acs.molpharmaceut.0c00714
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    Zs.A 6250: Show issues Location:
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  8. Article ; Online: Protease Activity Analysis: A Toolkit for Analyzing Enzyme Activity Data.

    Soleimany, Ava P / Martin-Alonso, Carmen / Anahtar, Melodi / Wang, Cathy S / Bhatia, Sangeeta N

    ACS omega

    2022  Volume 7, Issue 28, Page(s) 24292–24301

    Abstract: Analyzing the activity of proteases and their substrates is critical to defining the biological functions of these enzymes and to designing new diagnostics and therapeutics that target protease dysregulation in disease. While a wide range of databases ... ...

    Abstract Analyzing the activity of proteases and their substrates is critical to defining the biological functions of these enzymes and to designing new diagnostics and therapeutics that target protease dysregulation in disease. While a wide range of databases and algorithms have been created to better predict protease cleavage sites, there is a dearth of computational tools to automate analysis of
    Language English
    Publishing date 2022-07-06
    Publishing country United States
    Document type Journal Article
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.2c01559
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  9. Article ; Online: Ionic Liquid-Mediated Transdermal Delivery of Thrombosis-Detecting Nanosensors.

    Bekdemir, Ahmet / Tanner, Eden E L / Kirkpatrick, Jesse / Soleimany, Ava P / Mitragotri, Samir / Bhatia, Sangeeta N

    Advanced healthcare materials

    2022  Volume 11, Issue 11, Page(s) e2102685

    Abstract: Blood clotting disorders such as pulmonary embolism are associated with high morbidity and mortality. A large portion of thrombotic events occur postoperative and after hospital discharge. Therefore, easily applicable, noninvasive, and long-term ... ...

    Abstract Blood clotting disorders such as pulmonary embolism are associated with high morbidity and mortality. A large portion of thrombotic events occur postoperative and after hospital discharge. Therefore, easily applicable, noninvasive, and long-term monitoring of thrombosis occurrence is critical for urgent clinical intervention. Here, the use is proposed of ionic liquids as a skin transport facilitator to deliver thrombin-sensitive nanosensors that enable prolonged monitoring of pulmonary embolism. Co-formulation of nanosensors with choline and geranic acid (CAGE) ionic liquids demonstrates significant transdermal diffusion into the dermis of the skin and provides sustained release into the blood throughout 72 h. Upon reaching the systemic circulation, the nanosensors release reporter molecules into the urine by responding to activation of the clotting cascade and retain a diagnostic power for 24 h in an acute pulmonary embolism mouse model. These results demonstrate a proof-of-concept disease monitoring system that can be topically applied by patients and potentially reduce mortality and high cost of hospitalization.
    MeSH term(s) Administration, Cutaneous ; Animals ; Humans ; Ionic Liquids ; Mice ; Pulmonary Embolism ; Skin Absorption ; Thrombosis/drug therapy
    Chemical Substances Ionic Liquids
    Language English
    Publishing date 2022-02-27
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649576-4
    ISSN 2192-2659 ; 2192-2640
    ISSN (online) 2192-2659
    ISSN 2192-2640
    DOI 10.1002/adhm.202102685
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    Zs.A 6966: Show issues Location:
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  10. Article ; Online: Directing Cholangiocyte Morphogenesis in Natural Biomaterial Scaffolds.

    Smith, Quinton / Bays, Jennifer / Li, Linqing / Shareef, Haniyah / Chen, Christopher S / Bhatia, Sangeeta N

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2022  Volume 9, Issue 14, Page(s) e2201951

    Language English
    Publishing date 2022-05-12
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202201951
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