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  1. Article ; Online: Carrier-Free, Amorphous Verteporfin Nanodrug for Enhanced Photodynamic Cancer Therapy and Brain Drug Delivery.

    Quinlan, John A / Inglut, Collin T / Srivastava, Payal / Rahman, Idrisa / Stabile, Jillian / Gaitan, Brandon / Arnau Del Valle, Carla / Baumiller, Kaylin / Gaur, Anandita / Chiou, Wen-An / Karim, Baktiar / Connolly, Nina / Robey, Robert W / Woodworth, Graeme F / Gottesman, Michael M / Huang, Huang-Chiao

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2024  Volume 11, Issue 17, Page(s) e2302872

    Abstract: Glioblastoma (GBM) is hard to treat due to cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence is nearly universal even after surgery, chemotherapy, and radiation. Photodynamic therapy ( ... ...

    Abstract Glioblastoma (GBM) is hard to treat due to cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence is nearly universal even after surgery, chemotherapy, and radiation. Photodynamic therapy (PDT) involves photosensitizer administration followed by light activation to generate reactive oxygen species at tumor sites, thereby killing cells or inducing biological changes. PDT can ablate unresectable GBM and sensitize tumors to chemotherapy. Verteporfin (VP) is a promising photosensitizer that relies on liposomal carriers for clinical use. While lipids increase VP's solubility, they also reduce intracellular photosensitizer accumulation. Here, a pure-drug nanoformulation of VP, termed "NanoVP", eliminating the need for lipids, excipients, or stabilizers is reported. NanoVP has a tunable size (65-150 nm) and 1500-fold higher photosensitizer loading capacity than liposomal VP. NanoVP shows a 2-fold increase in photosensitizer uptake and superior PDT efficacy in GBM cells compared to liposomal VP. In mouse models, NanoVP-PDT improved tumor control and extended animal survival, outperforming liposomal VP and 5-aminolevulinic acid (5-ALA). Moreover, low-dose NanoVP-PDT can safely open the blood-brain barrier, increasing drug accumulation in rat brains by 5.5-fold compared to 5-ALA. NanoVP is a new photosensitizer formulation that has the potential to facilitate PDT for the treatment of GBM.
    MeSH term(s) Animals ; Photochemotherapy/methods ; Verteporfin/pharmacology ; Verteporfin/therapeutic use ; Mice ; Photosensitizing Agents/administration & dosage ; Photosensitizing Agents/pharmacology ; Brain Neoplasms/drug therapy ; Drug Delivery Systems/methods ; Glioblastoma/drug therapy ; Nanoparticles/chemistry ; Disease Models, Animal ; Humans ; Rats ; Liposomes ; Cell Line, Tumor ; Brain/metabolism ; Brain/drug effects
    Chemical Substances Verteporfin (0X9PA28K43) ; Photosensitizing Agents ; Liposomes
    Language English
    Publishing date 2024-03-06
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202302872
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Photodynamic Priming Modulates Endothelial Cell-Cell Junction Phenotype for Light-activated Remote Control of Drug Delivery.

    Inglut, Collin T / Gray, Kelsey M / Vig, Shruti / Jung, Jae W / Stabile, Jillian / Zhang, Yuji / Stroka, Kimberly M / Huang, Huang-Chiao

    IEEE journal of selected topics in quantum electronics : a publication of the IEEE Lasers and Electro-optics Society

    2020  Volume 27, Issue 4

    Abstract: The blood-brain barrier (BBB) remains a major obstacle for drug delivery to the central nervous system. In particular, the tight and adherens junctions that join the brain capillary endothelial cells limit the diffusion of various molecules from the ... ...

    Abstract The blood-brain barrier (BBB) remains a major obstacle for drug delivery to the central nervous system. In particular, the tight and adherens junctions that join the brain capillary endothelial cells limit the diffusion of various molecules from the bloodstream into the brain. Photodynamic priming (PDP) is a non-cytotoxic modality that involves light activation of photosensitizers to photochemically modulate nearby molecules without killing the cells. Here we investigate the effects of sub-lethal photochemistry on junction phenotype (i.e., continuous, punctate, or perpendicular), as well as the BBB permeability in a transwell model of human brain microvascular endothelial cells (HBMECs). We showed that PDP decreases the continuous junction architecture by ~20%, increases the perpendicular junction architecture by ~40%, and has minimal impact on cell morphology in HBMECs. Furthermore, transwell permeability assay revealed that PDP improves the HBMEC permeability to dextran or nanoliposomes by up to 30-fold for 6-9 days. These results suggest that PDP could safely reverse the mature brain endothelial junctions without killing the HBMECs. This study not only emphasizes the critical roles of PDP in the modulation junction phenotype, but also highlights the opportunity to further develop PDP-based combinations that opens the cerebrum endothelium for enhanced drug transporter across the BBB.
    Language English
    Publishing date 2020-09-15
    Publishing country United States
    Document type Journal Article
    ISSN 1077-260X
    ISSN 1077-260X
    DOI 10.1109/jstqe.2020.3024014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Systematic Evaluation of Light-Activatable Biohybrids for Anti-Glioma Photodynamic Therapy.

    Inglut, Collin T / Baglo, Yan / Liang, Barry J / Cheema, Yahya / Stabile, Jillian / Woodworth, Graeme F / Huang, Huang-Chiao

    Journal of clinical medicine

    2019  Volume 8, Issue 9

    Abstract: Photosensitizing biomolecules (PSBM) represent a new generation of light-absorbing compounds with improved optical and physicochemical properties for biomedical applications. Despite numerous advances in lipid-, polymer-, and protein-based PSBMs, their ... ...

    Abstract Photosensitizing biomolecules (PSBM) represent a new generation of light-absorbing compounds with improved optical and physicochemical properties for biomedical applications. Despite numerous advances in lipid-, polymer-, and protein-based PSBMs, their effective use requires a fundamental understanding of how macromolecular structure influences the physicochemical and biological properties of the photosensitizer. Here, we prepared and characterized three well-defined PSBMs based on a clinically used photosensitizer, benzoporphyrin derivative (BPD). The PSBMs include 16:0 lysophosphocholine-BPD (16:0 Lyso PC-BPD), distearoyl-phosphoethanolamine-polyethylene-glycol-BPD (DSPE-PEG-BPD), and anti-EGFR cetuximab-BPD (Cet-BPD). In two glioma cell lines, DSPE-PEG-BPD exhibited the highest singlet oxygen yield but was the least phototoxic due to low cellular uptake. The 16:0 Lyso PC-BPD was most efficient in promoting cellular uptake but redirected BPD's subcellular localization from mitochondria to lysosomes. At 24 h after incubation, proteolyzed Cet-BPD was localized to mitochondria and effectively disrupted the mitochondrial membrane potential upon light activation. Our results revealed the variable trafficking and end effects of PSBMs, providing valuable insights into methods of PSBM evaluation, as well as strategies to select PSBMs based on subcellular targets and cytotoxic mechanisms. We demonstrated that biologically informed combinations of PSBMs to target lysosomes and mitochondria, concurrently, may lead to enhanced therapeutic effects against gliomas.
    Language English
    Publishing date 2019-08-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm8091269
    Database MEDical Literature Analysis and Retrieval System OnLINE

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