Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy. Nat Commun 2020 Nov 10;11(1):5687
Date
11/12/2020Pubmed ID
33173024Pubmed Central ID
PMC7655867DOI
10.1038/s41467-020-19225-7Scopus ID
2-s2.0-85095757925 (requires institutional sign-in at Scopus site) 271 CitationsAbstract
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.
Author List
Gregory JV, Kadiyala P, Doherty R, Cadena M, Habeel S, Ruoslahti E, Lowenstein PR, Castro MG, Lahann JAuthor
Samer Habeel MD Instructor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood-Brain Barrier
Brain Neoplasms
Cell Line, Tumor
Drug Delivery Systems
Gene Silencing
Glioblastoma
Humans
Mice
Nanoparticles
RNA, Small Interfering
STAT3 Transcription Factor
