Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy

Jason V. Gregory, Padma Kadiyala, Robert Doherty, Melissa Cadena, Samer Habeel, Erkki Ruoslahti, Pedro R. Lowenstein, Maria G. Castro () and Joerg Lahann ()
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Jason V. Gregory: Biointerfaces Institute, University of Michigan
Padma Kadiyala: University of Michigan Medical School
Robert Doherty: University of Michigan Medical School
Melissa Cadena: Biointerfaces Institute, University of Michigan
Samer Habeel: Biointerfaces Institute, University of Michigan
Erkki Ruoslahti: Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute
Pedro R. Lowenstein: Biointerfaces Institute, University of Michigan
Maria G. Castro: Biointerfaces Institute, University of Michigan
Joerg Lahann: Biointerfaces Institute, University of Michigan

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19225-7

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