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Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy

Author

Listed:
  • Jason V. Gregory

    (Biointerfaces Institute, University of Michigan
    Chemical Engineering, University of Michigan)

  • Padma Kadiyala

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Robert Doherty

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Melissa Cadena

    (Biointerfaces Institute, University of Michigan
    Biomedical Engineering, University of Michigan)

  • Samer Habeel

    (Biointerfaces Institute, University of Michigan
    Biomedical Engineering, University of Michigan)

  • Erkki Ruoslahti

    (Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
    University of California, Santa Barbara)

  • Pedro R. Lowenstein

    (Biointerfaces Institute, University of Michigan
    University of Michigan Medical School
    University of Michigan Medical School)

  • Maria G. Castro

    (Biointerfaces Institute, University of Michigan
    University of Michigan Medical School
    University of Michigan Medical School)

  • Joerg Lahann

    (Biointerfaces Institute, University of Michigan
    Chemical Engineering, University of Michigan
    Biomedical Engineering, University of Michigan)

Abstract

Glioblastoma (GBM), the most aggressive form of brain cancer, has witnessed very little clinical progress over the last decades, in part, due to the absence of effective drug delivery strategies. Intravenous injection is the least invasive drug delivery route to the brain, but has been severely limited by the blood-brain barrier (BBB). Inspired by the capacity of natural proteins and viral particulates to cross the BBB, we engineered a synthetic protein nanoparticle (SPNP) based on polymerized human serum albumin (HSA) equipped with the cell-penetrating peptide iRGD. SPNPs containing siRNA against Signal Transducer and Activation of Transcription 3 factor (STAT3i) result in in vitro and in vivo downregulation of STAT3, a central hub associated with GBM progression. When combined with the standard of care, ionized radiation, STAT3i SPNPs result in tumor regression and long-term survival in 87.5% of GBM-bearing mice and prime the immune system to develop anti-GBM immunological memory.

Suggested Citation

  • Jason V. Gregory & Padma Kadiyala & Robert Doherty & Melissa Cadena & Samer Habeel & Erkki Ruoslahti & Pedro R. Lowenstein & Maria G. Castro & Joerg Lahann, 2020. "Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19225-7
    DOI: 10.1038/s41467-020-19225-7
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    Cited by:

    1. Hao Li & Meng Wang & Biao Huang & Su-Wen Zhu & Jun-Jie Zhou & De-Run Chen & Ran Cui & Mingxi Zhang & Zhi-Jun Sun, 2021. "Theranostic near-infrared-IIb emitting nanoprobes for promoting immunogenic radiotherapy and abscopal effects against cancer metastasis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Weiwei Lin & Rui Niu & Seong-Min Park & Yan Zou & Sung Soo Kim & Xue Xia & Songge Xing & Qingshan Yang & Xinhong Sun & Zheng Yuan & Shuchang Zhou & Dongya Zhang & Hyung Joon Kwon & Saewhan Park & Chan, 2023. "IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Imran Noorani & Jorge Rosa, 2023. "Breaking barriers for glioblastoma with a path to enhanced drug delivery," Nature Communications, Nature, vol. 14(1), pages 1-4, December.

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