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Carrier-Free, Amorphous Verteporfin Nanodrug for Enhanced Photodynamic Cancer Therapy and Brain Drug Delivery

  1. Author:
    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 [ORCID]

  2. Author Address

    Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA., Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA., Advanced Imaging and Microscopy Laboratory, Maryland Nano Center, University of Maryland, College Park, MD, 20742, USA., Molecular Histopathology Laboratory, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA., Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201, USA., Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.,
    1. Year: 2024
    2. Date: Mar 06
    3. Epub Date: 2024 03 06
  2. Journal: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
    1. Pages: e2302872
  4. Type of Article: Article
  5. Article Number: e2302872
  1. 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. © 2024 The Authors. Advanced Science published by Wiley-VCH GmbH.

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  2. DOI: 10.1002/advs.202302872
  3. PMID: 38445882

Library Notes

  1. Fiscal Year: FY2023-2024
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