Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH-dependent cell interaction, internalization and cytotoxicity in vitro.
The cytotoxicity of adriamycin (ADR)-loaded and pH-sensitive nanoparticles made of pullulan acetate (PA) and sulfonamide (sulfadimethoxine; SDM) (PA/SDM) conjugate to a breast tumor cell line (MCF-7) was investigated to test the feasibility of the nanoparticles in targeting acidic tumor extracellular pH (pH(e)). At pH 6.8, ADR loaded PA/SDM nanoparticles showed cytotoxicity in the cell culture experiment, comparable to that of free ADR at the same ADR concentrations, while the relative cytotoxicity at pH 7.4 was low at the tested concentration range. This pronounced cytotoxicity of the nanoparticles at low pH was attributed to the accelerated release of ADR triggered by pH, enhanced interaction with cells, and internalization. At pH 6.8 and 6.4, the PA/SDM nanoparticles aggressively bounded to MCF-7 cells, probably due to interactions of the cells with hydrophobized nanoparticle surfaces caused by SDM deionization. A confocal laser microscopic study revealed intracellular localization of the drug-loaded nanoparticles. Based on these findings, the pH-sensitive nanoparticles deserve further investigation with an in vivo animal model as a targeted carrier of pH(e).
Na
Kun
K
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 315, Salt Lake City, UT 84108, USA.
Lee
Eun Seong
ES
Bae
You Han
YH
D000085:Acetates / Q000493:pharmacokinetics* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000633:toxicity; D005936:Glucans / Q000493:pharmacokinetics* / Q000633:toxicity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036103:Nanotechnology / Q000379:methods*; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000085:Acetates; D005936:Glucans; D013449:Sulfonamides; D004317:Doxorubicin; C009109:pullulan