Document Detail


Effect of cationic side-chains on intracellular delivery and cytotoxicity of pH sensitive polymer-doxorubicin nanocarriers.
MedLine Citation:
PMID:  23041969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fine-tuning the design of polymer-doxorubicin conjugates permits optimization of an efficient nanocarrier to greatly increase intracellular uptake and cytotoxicity. Here, we report synthesis of a family of self-assembled polymer-doxorubicin nanoparticles and an evaluation of the effects of various types of side-chains on intracellular uptake and cytotoxicity of the nanocarriers for lymphoma cells. Monomers with three different cationic side-chains (CA) and pK(a)'s, i.e., a guanidinium group (Ag), an imidazole group (Im), and a tertiary amine group (Dm), were comparatively investigated. The cationic monomer, poly(ethylene glycol) (PEG), and doxorubicin (Dox) were reacted with 1,4-(butanediol) diacrylate (BUDA) to prepare a poly(β-amino ester) (PBAE) polymer via Michael addition. All three polymer-Dox conjugates spontaneously formed nanoparticles (NP) through hydrophobic interactions between doxorubicin in aqueous solution, resulting in NP-Im/Dox, NP-Ag/Dox, and NP-Dm/Dox, with hydrodynamic sizes below 80 nm. Doxorubicin was linked to all 3 types of NPs with a hydrazone bond to assure selective release of doxorubicin only at acidic pH, as it occurs in the tumor microenvironment. Both NP-Im/Dox and NP-Ag/Dox exhibited much higher intracellular uptake by Ramos cells (Burkitt's lymphoma) than NP-Dm/Dox, suggesting that the type of side chain in the NPs determines the extent of intracellular uptake. As a result, NP-Im/Dox and NP-Ag/Dox showed cytotoxicity that was comparable to free Dox in vitro. Our findings suggest that the nature of surface cationic group on nanocarriers may profoundly influence their intracellular trafficking and resulting therapeutic efficacy. Thus, it is a crucial factor to be considered in the design of novel carriers for intracellular drug delivery.
Authors:
Chen Fang; Forrest M Kievit; Yong-Chan Cho; Hyejung Mok; Oliver W Press; Miqin Zhang
Related Documents :
22374069 - Interaction of monogalactosyldiacylglycerol with cytochrome b(6)f complex in surface fi...
24581849 - The cpp-acp relieved enamel erosion from a carbonated soft beverage: an in vitro afm an...
1267619 - The sink action of cerebrospinal fluid volume flow. effect on brain water content.
20009379 - Electrical conductivity of orthopyroxene: implications for the water content of the ast...
23226709 - Two new species of tornidae (caenogastropoda, rissooidea) from espírito santo, brazil.
25462979 - A triticale water-deficit-inducible phytocystatin inhibits endogenous cysteine proteina...
10882499 - Association of molybdenum ionic species with alumina surface.
22861859 - Take off of small leidenfrost droplets.
23914939 - Interface chemistry guided long-cycle-life li-s battery.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Nanoscale     Volume:  4     ISSN:  2040-3372     ISO Abbreviation:  Nanoscale     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-30     Completed Date:  2013-04-09     Revised Date:  2013-08-30    
Medline Journal Info:
Nlm Unique ID:  101525249     Medline TA:  Nanoscale     Country:  England    
Other Details:
Languages:  eng     Pagination:  7012-20     Citation Subset:  IM    
Affiliation:
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cations / chemistry
Cell Line, Tumor
Cell Survival / drug effects
Doxorubicin / chemistry*,  toxicity
Drug Carriers / chemistry*
Humans
Hydrazones / chemistry
Hydrogen-Ion Concentration
Metal Nanoparticles / chemistry*
Microscopy, Confocal
Polyethylene Glycols / chemistry
Polymers / chemistry*
Silver / chemistry
Grant Support
ID/Acronym/Agency:
P30 CA015704/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cations; 0/Drug Carriers; 0/Hydrazones; 0/Polyethylene Glycols; 0/Polymers; 0/poly(beta-amino ester); 23214-92-8/Doxorubicin; 7440-22-4/Silver

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


Previous Document:  Is the Deleterious Effect of Cryotherapy on Proprioception Mitigated by Exercise?
Next Document:  Aire mediates thymic expression and tolerance of pancreatic antigens via an unconventional transcrip...