Systemic brain tumor delivery of synthetic protein nanoparticles for glioblastoma therapy
| Autor: | Melissa Cadena, Erkki Ruoslahti, Robert Doherty, Padma Kadiyala, Maria G. Castro, Samer Habeel, Joerg Lahann, Jason V. Gregory, Pedro R. Lowenstein |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Science Brain tumor General Physics and Astronomy Blood–brain barrier Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Immune system Downregulation and upregulation In vivo Cell Line Tumor Animals Humans Gene silencing Medicine Gene Silencing RNA Small Interfering STAT3 lcsh:Science Multidisciplinary biology Brain Neoplasms business.industry Bioinspired materials General Chemistry medicine.disease In vitro nervous system diseases CNS cancer 030104 developmental biology medicine.anatomical_structure Blood-Brain Barrier 030220 oncology & carcinogenesis Drug delivery Cancer research biology.protein Nanoparticles lcsh:Q Signal transduction Glioblastoma business |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The lack of effective drug delivery strategies has impaired the therapeutic progress in the treatment of glioblastoma (GBM). Here, the authors engineer synthetic protein nanoparticle based on polymerized human serum albumin equipped with the cell-penetrating peptide iRGD to deliver siRNA against STAT3 and report improved survival in a mouse model of GBM. |
| Databáze: | OpenAIRE |
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