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Article: "Alternative" endocytic mechanisms exploited by pathogens: new avenues for therapeutic delivery?

Medina-Kauwe, L K

2007 Volume 59, Issue 8, Page(s) 798–809

Abstract: Some pathogens utilize unique routes to enter cells that may evade the intracellular barriers encountered by the typical clathrin-mediated endocytic pathway. Retrograde transport and caveolar uptake are among the better characterized pathways, as ... ...

Abstract	Some pathogens utilize unique routes to enter cells that may evade the intracellular barriers encountered by the typical clathrin-mediated endocytic pathway. Retrograde transport and caveolar uptake are among the better characterized pathways, as alternatives to clathrin-mediated endocytosis, that are known to facilitate entry of pathogens and potential delivery agents. Recent characterization of the trafficking mechanisms of prion proteins and certain bacteria may present new paradigms for strategizing improvements in therapeutic spread and retention of therapy. This review will provide an overview of such endocytic pathways, and discuss current and future possibilities in using these routes as a means to improve therapeutic delivery.
MeSH term(s)	Animals ; Bacterial Toxins/metabolism ; Biological Transport ; Caveolae/metabolism ; Caveolae/microbiology ; Clathrin/chemistry ; Clathrin/metabolism ; Clathrin-Coated Vesicles/metabolism ; Coated Pits, Cell-Membrane/chemistry ; Coated Pits, Cell-Membrane/metabolism ; Drug Delivery Systems ; Endocytosis/physiology ; Endoplasmic Reticulum/metabolism ; Endosomes/chemistry ; Endosomes/metabolism ; Golgi Apparatus/chemistry ; Golgi Apparatus/metabolism ; Intracellular Signaling Peptides and Proteins ; Prions/chemistry ; Prions/metabolism ; Toxins, Biological/chemistry ; Toxins, Biological/metabolism ; Vesicular Transport Proteins/metabolism ; trans-Golgi Network/chemistry ; trans-Golgi Network/metabolism
Chemical Substances	Bacterial Toxins ; Clathrin ; Intracellular Signaling Peptides and Proteins ; Prions ; Toxins, Biological ; Vesicular Transport Proteins
Keywords	covid19
Language	English
Publishing date	2007-07-05
Publishing country	Netherlands
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. ; Review
ZDB-ID	639113-8
ISSN	1872-8294 ; 0169-409X
ISSN (online)	1872-8294
ISSN	0169-409X
DOI	10.1016/j.addr.2007.06.009
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Article: Introduction to the special issue: traveling the intracellular highway to gene therapy.

Medina-Kauwe, L K

Gene therapy

2005 Volume 12, Issue 11, Page(s) 863–864

MeSH term(s)	Gene Transfer Techniques ; Genetic Therapy/methods ; Genetic Vectors/pharmacokinetics ; Humans ; Signal Transduction
Language	English
Publishing date	2005-06
Publishing country	England
Document type	Editorial
ZDB-ID	1191036-7
ISSN	1476-5462 ; 0969-7128
ISSN (online)	1476-5462
ISSN	0969-7128
DOI	10.1038/sj.gt.3302551
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Zs.A 3991: Show issues

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Article ; Online: Analysis of targeted viral protein nanoparticles delivered to HER2+ tumors.

Hwang, Jae Youn / Farkas, Daniel L / Medina-Kauwe, Lali K

Journal of visualized experiments : JoVE

2013 , Issue 76

Abstract: The HER2+ tumor-targeted nanoparticle, HerDox, exhibits tumor-preferential accumulation and tumor-growth ablation in an animal model of HER2+ cancer. HerDox is formed by non-covalent self-assembly of a tumor targeted cell penetration protein with the ... ...

Abstract	The HER2+ tumor-targeted nanoparticle, HerDox, exhibits tumor-preferential accumulation and tumor-growth ablation in an animal model of HER2+ cancer. HerDox is formed by non-covalent self-assembly of a tumor targeted cell penetration protein with the chemotherapy agent, doxorubicin, via a small nucleic acid linker. A combination of electrophilic, intercalation, and oligomerization interactions facilitate self-assembly into round 10-20 nm particles. HerDox exhibits stability in blood as well as in extended storage at different temperatures. Systemic delivery of HerDox in tumor-bearing mice results in tumor-cell death with no detectable adverse effects to non-tumor tissue, including the heart and liver (which undergo marked damage by untargeted doxorubicin). HER2 elevation facilitates targeting to cells expressing the human epidermal growth factor receptor, hence tumors displaying elevated HER2 levels exhibit greater accumulation of HerDox compared to cells expressing lower levels, both in vitro and in vivo. Fluorescence intensity imaging combined with in situ confocal and spectral analysis has allowed us to verify in vivo tumor targeting and tumor cell penetration of HerDox after systemic delivery. Here we detail our methods for assessing tumor targeting via multimode imaging after systemic delivery.
MeSH term(s)	Animals ; Antibiotics, Antineoplastic/administration & dosage ; Antibiotics, Antineoplastic/chemistry ; Antibiotics, Antineoplastic/pharmacokinetics ; Breast Neoplasms/drug therapy ; Breast Neoplasms/enzymology ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Doxorubicin/administration & dosage ; Doxorubicin/chemistry ; Doxorubicin/pharmacokinetics ; Drug Stability ; Female ; Humans ; Mice ; Mice, Nude ; Microscopy, Fluorescence/methods ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Receptor, ErbB-2/metabolism ; Xenograft Model Antitumor Assays
Chemical Substances	Antibiotics, Antineoplastic ; Doxorubicin (80168379AG) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2013-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/50396
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Article: Large Field of View Scanning Fluorescence Lifetime Imaging System for Multimode Optical Imaging of Small Animals.

Hwang, Jae Youn / Agadjanian, Hasmik / Medina-Kauwe, Lali K / Gross, Zeev / Gray, Harry B / Sorasaenee, Karn / Farkas, Daniel L

Proceedings of SPIE--the International Society for Optical Engineering

2017 Volume 6859

Abstract: We describe a scanning fluorescence lifetime imaging (SFLIM) system that provides a large field of view (LFOV), using a femtosecond (fs) pulsed laser, for multi-mode optical imaging of small animals. Fluorescence lifetime imaging (FLIM) can be a useful ... ...

Abstract	We describe a scanning fluorescence lifetime imaging (SFLIM) system that provides a large field of view (LFOV), using a femtosecond (fs) pulsed laser, for multi-mode optical imaging of small animals. Fluorescence lifetime imaging (FLIM) can be a useful optical method to distinguish between fluorophores inside small animals. However, difficulty arises when LFOV is required in FLIM using a fs pulsed laser for the excitation of the fluorophores at low wavelengths (<500nm), primarily because the field of view of the pulsed blue excitation light generated from the second harmonic of the fs pulsed light is limited to about a centimeter in diameter due to the severe scattering and absorption of the light inside tissues. Here, we choose a scanning method in order to acquire a FLIM image with LFOV as one alternative. In the SFLIM system, we used a conventional cooled CCD camera coupled to an ultra-fast time-gated intensifier, a tunable femtosecond laser for the excitation of fluorophores, and an x-y moving stage for scanning. Images acquired through scanning were combined into a single image and then this reconstructed image was compared with images obtained by spectral imaging. The resulting SFLIM system is promising as an alternative method for the FLIM imaging of small animals, containing fluorophores exited by blue light, for LFOV applications such as whole animal imaging.
Language	English
Publishing date	2017-12-18
Publishing country	United States
Document type	Journal Article
ISSN	0277-786X
ISSN	0277-786X
DOI	10.1117/12.769305
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Article ; Online: Novel potent azetidine-based compounds irreversibly inhibit Stat3 activation and induce antitumor response against human breast tumor growth in vivo.

Cancer letters

2022 Volume 534, Page(s) 215613

Abstract: Signal transducer and activator of transcription (Stat)3 is a valid anticancer therapeutic target. We have discovered a highly potent chemotype that amplifies the Stat3-inhibitory activity of lead compounds to levels previously unseen. The azetidine- ... ...

Abstract	Signal transducer and activator of transcription (Stat)3 is a valid anticancer therapeutic target. We have discovered a highly potent chemotype that amplifies the Stat3-inhibitory activity of lead compounds to levels previously unseen. The azetidine-based compounds, including H172 (9f) and H182, irreversibly bind to Stat3 and selectively inhibit Stat3 activity (IC
MeSH term(s)	Animals ; Apoptosis ; Azetidines/pharmacology ; Cell Line, Tumor ; Humans ; Mice ; Phosphorylation ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics
Chemical Substances	Azetidines ; STAT3 Transcription Factor ; STAT3 protein, human ; azetidine (37S883XDWR)
Language	English
Publishing date	2022-03-09
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2022.215613
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Zs.A 1177: Show issues

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Article: Multimode Optical Imaging for Translational Chemotherapy: In Vivo Tumor Detection and Delineation by Targeted Gallium Corroles.

Hwang, Jae Youn / Gross, Zeev / Gray, Harry B / Medina-Kauwe, Lali K / Farkas, Daniel L

Proceedings of SPIE--the International Society for Optical Engineering

2014 Volume 7902

Abstract: We report the feasibility of tumor detection and ... ...

Abstract	We report the feasibility of tumor detection and delineation
Language	English
Publishing date	2014-10-17
Publishing country	United States
Document type	Journal Article
ISSN	0277-786X
ISSN	0277-786X
DOI	10.1117/12.877780
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Article ; Online: Discovery of Novel Azetidine Amides as Potent Small-Molecule STAT3 Inhibitors.

Brotherton-Pleiss, Christine / Yue, Peibin / Zhu, Yinsong / Nakamura, Kayo / Chen, Weiliang / Fu, Wenzhen / Kubota, Casie / Chen, Jasmine / Alonso-Valenteen, Felix / Mikhael, Simoun / Medina-Kauwe, Lali / Tius, Marcus A / Lopez-Tapia, Francisco / Turkson, James

Journal of medicinal chemistry

2020 Volume 64, Issue 1, Page(s) 695–710

Abstract: We optimized our previously reported proline-based STAT3 inhibitors into an exciting new series of ( ...

Abstract	We optimized our previously reported proline-based STAT3 inhibitors into an exciting new series of (
MeSH term(s)	Amides/chemistry ; Apoptosis/drug effects ; Azetidines/chemistry ; Azetidines/metabolism ; Azetidines/pharmacology ; Cell Line, Tumor ; Cell Survival/drug effects ; DNA/chemistry ; DNA/metabolism ; Drug Evaluation, Preclinical ; Humans ; Inhibitory Concentration 50 ; Phosphorylation/drug effects ; Protein Binding ; STAT3 Transcription Factor/antagonists & inhibitors ; STAT3 Transcription Factor/metabolism ; Structure-Activity Relationship
Chemical Substances	Amides ; Azetidines ; STAT3 Transcription Factor ; STAT3 protein, human ; DNA (9007-49-2)
Language	English
Publishing date	2020-12-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.0c01705
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Zs.B 151: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging.

Hwang, Jae Youn / Lubow, Jay / Chu, David / Gross, Zeev / Gray, Harry B / Farkas, Daniel L / Medina-Kauwe, Lali K

Proceedings of SPIE--the International Society for Optical Engineering

2014 Volume 7886

Abstract: We recently developed a novel therapeutic particle, HerGa, for breast cancer treatment and detection. HerGa consists of a tumor-targeted cell penetration protein noncovalently assembled with a gallium-metallated corrole. The corrole is structurally ... ...

Abstract	We recently developed a novel therapeutic particle, HerGa, for breast cancer treatment and detection. HerGa consists of a tumor-targeted cell penetration protein noncovalently assembled with a gallium-metallated corrole. The corrole is structurally similar to porphyrin, emits intense fluorescence, and has proven highly effective for breast tumor treatment preclinically, without light exposure. Here, we tested HerGa as a photosensitizer for photodynamic therapy and investigated its mechanism of action using multimode optical imaging. Using confocal fluorescence imaging, we observed that HerGa disrupts the mitochondrial membrane potential
Language	English
Publishing date	2014-11-18
Publishing country	United States
Document type	Journal Article
ISSN	0277-786X
ISSN	0277-786X
DOI	10.1117/12.873337
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Article ; Online: Ratiometric spectral imaging for fast tumor detection and chemotherapy monitoring in vivo.

Hwang, Jae Youn / Gross, Zeev / Gray, Harry B / Medina-Kauwe, Lali K / Farkas, Daniel L

Journal of biomedical optics

2011 Volume 16, Issue 6, Page(s) 66007

Abstract: We report a novel in vivo spectral imaging approach to cancer detection and chemotherapy assessment. We describe and characterize a ratiometric spectral imaging and analysis method and evaluate its performance for tumor detection and delineation by ... ...

Abstract	We report a novel in vivo spectral imaging approach to cancer detection and chemotherapy assessment. We describe and characterize a ratiometric spectral imaging and analysis method and evaluate its performance for tumor detection and delineation by quantitatively monitoring the specific accumulation of targeted gallium corrole (HerGa) into HER2-positive (HER2 +) breast tumors. HerGa temporal accumulation in nude mice bearing HER2 + breast tumors was monitored comparatively by a. this new ratiometric imaging and analysis method; b. established (reflectance and fluorescence) spectral imaging; c. more commonly used fluorescence intensity imaging. We also tested the feasibility of HerGa imaging in vivo using the ratiometric spectral imaging method for tumor detection and delineation. Our results show that the new method not only provides better quantitative information than typical spectral imaging, but also better specificity than standard fluorescence intensity imaging, thus allowing enhanced in vivo outlining of tumors and dynamic, quantitative monitoring of targeted chemotherapy agent accumulation into them.
MeSH term(s)	Algorithms ; Animals ; Contrast Media/pharmacokinetics ; Drug Monitoring/methods ; Female ; Gallium/pharmacokinetics ; Mice ; Mice, Nude ; Molecular Imaging/methods ; Neoplasms/drug therapy ; Neoplasms/enzymology ; Neoplasms/metabolism ; Neoplasms/pathology ; Receptor, ErbB-2/biosynthesis ; Spectrometry, Fluorescence ; Transplantation, Heterologous
Chemical Substances	Contrast Media ; Gallium (CH46OC8YV4) ; Erbb2 protein, mouse (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2011-07-15
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	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.3589299
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Zs.A 4699: Show issues

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Article ; Online: Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.

Hwang, Jae Youn / Park, Jinhyoung / Kang, Bong Jin / Lubow, David J / Chu, David / Farkas, Daniel L / Shung, K Kirk / Medina-Kauwe, Lali K

PloS one

2012 Volume 7, Issue 4, Page(s) e34463

Abstract: This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess ... ...

Abstract	This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Doxorubicin/chemistry ; Doxorubicin/metabolism ; Doxorubicin/pharmacology ; Drug Screening Assays, Antitumor ; Female ; Humans ; Mice ; Molecular Imaging/methods ; Molecular Targeted Therapy ; Nanoparticles ; Receptor, ErbB-2/metabolism ; Spectrometry, Fluorescence ; Treatment Outcome ; Ultrasonics
Chemical Substances	Doxorubicin (80168379AG) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2012-04-03
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.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0034463
Database	MEDical Literature Analysis and Retrieval System OnLINE

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