| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Proceedings of the National Academy of Sciences | ||||
| Publisher: | NATL ACAD SCIENCES | ||||
| Place of Publication: | WASHINGTON | ||||
| Volume: | 107 | ||||
| Number of Issue or Book Chapter: | 42 | ||||
| Page Range: | pp. 18143-18148 | ||||
| Date: | 2010 | ||||
| Institutions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Alumni or Retired > Prof. Dr. Eggehard Holler | ||||
| Identification Number: |
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| Keywords: | GENE DELIVERY; IN-VIVO; MALIGNANT GLIOMAS; HPMA COPOLYMER; BARRIER; PEPTIDE; ANGIOGENESIS; PERMEABILITY; CHEMOTHERAPY; LAMININ-8; glioma treatment; polymalic acid; laminin-411; endosomal escape; blood-brain barrier | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 65666 |
Web of ScienceAbstract
Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood-brain barrier (BBB) or blood-brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic ...
Abstract
Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood-brain barrier (BBB) or blood-brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v. treatment of brain tumors. The polymeric drug passes through the BTB and tumor cell membrane using tandem monoclonal antibodies targeting the BTB and tumor cells. The next step for polymeric drug action was inhibition of tumor angiogenesis by specifically blocking the synthesis of a tumor neovascular trimer protein, laminin-411, by attached antisense oligonucleotides (AONs). The AONs were released into the target cell cytoplasm via pH-activated trileucine, an endosomal escape moiety. Drug delivery to the brain tumor and the release mechanism were both studied for this nanobiopolymer. Introduction of a trileucine endosome escape unit resulted in significantly increased AON delivery to tumor cells, inhibition of laminin-411 synthesis in vitro and in vivo, specific accumulation in brain tumors, and suppression of intracranial glioma growth compared with pH-independent leucine ester. The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy of glioma treatment. This delivery system with drug release into the brain-specific cell type could be useful for treatment of various brain pathologies.
Metadata last modified: 19 Dec 2024 11:32
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