Document Detail


Toward intracellular targeted delivery of cancer therapeutics: progress and clinical outlook for brain tumor therapy.
MedLine Citation:
PMID:  22671766     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells.
Authors:
Hetal Pandya; Waldemar Debinski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy     Volume:  26     ISSN:  1173-8804     ISO Abbreviation:  BioDrugs     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-04     Completed Date:  2012-12-17     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  9705305     Medline TA:  BioDrugs     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  235-44     Citation Subset:  IM    
Affiliation:
The Brain Tumor Center of Excellence, Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / administration & dosage*,  therapeutic use
Bacterial Toxins / chemistry
Brain Neoplasms / drug therapy*,  metabolism,  pathology
Cell Nucleus / metabolism
Cytoplasm / metabolism
Drug Carriers / chemistry
Drug Delivery Systems / methods*
Glioblastoma / drug therapy*,  metabolism,  pathology
Humans
Interleukin-13 Receptor alpha2 Subunit / genetics,  metabolism
Ligands
Peptides / chemistry
Protein Engineering
Radioisotopes
Recombinant Fusion Proteins / chemistry,  genetics
Grant Support
ID/Acronym/Agency:
R01 CA074145/CA/NCI NIH HHS; R01 CA74145/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Bacterial Toxins; 0/Drug Carriers; 0/Interleukin-13 Receptor alpha2 Subunit; 0/KLA peptide; 0/Ligands; 0/Peptides; 0/Radioisotopes; 0/Recombinant Fusion Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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