Nitric oxide-releasing silica nanoparticle inhibition of ovarian cancer cell growth.
Although the potent antitumor activity of nitric oxide (NO) supports its promise as an antineoplastic agent, effective and selective delivery and action on tumor and not normal cells remains a limiting factor. Nanoparticle-based delivery of NO has been considered as one approach to overcome these limitations. Therefore, we determined the utility of NO delivery using silica nanoparticles and evaluated their antitumor efficacy against human ovarian tumor and nontumor cells. The NO-releasing nanoparticles exhibited enhanced growth inhibition of ovarian tumor cells when compared to both control nanoparticles and a previously reported small molecule NO donor, PYRRO/NO. In addition, the NO-releasing nanoparticles showed greater inhibition of the anchorage-independent growth of tumor-derived and Ras-transformed ovarian cells. Confocal microscopy analysis revealed that fluorescently labeled NO-releasing nanoparticles entered the cytosol of the cell and localized to late endosomes and lysosomes. Furthermore, we observed a nanoparticle size dependency on efficacy against normal versus transformed ovarian cells. Our study provides the first application of nanoparticle-derived NO as an antitumor therapy and merits future studies examining nanoparticle formulation for in vivo applications.
Stevens
Ellen V
EV
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Carpenter
Alexis W
AW
Shin
Jae Ho
JH
Liu
Jinsong
J
Der
Channing J
CJ
Schoenfisch
Mark H
MH
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011759:Pyrrolidines / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*
D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D011759:Pyrrolidines; D009569:Nitric Oxide; D012822:Silicon Dioxide; C032519:pyrrolidine