Abstract
Cisplatin is used to treat a variety of tumors, but dose-limiting toxicities or intrinsic and acquired resistance limit its application in many types of cancer including breast. Cisplatin was attached to silica nanoparticles using aminopropyltriethoxy silane as a linker molecule and characterized in terms of size, shape, as well as the dissolution of cisplatin from the silica surface. The primary particle diameter of the as received silica nanoparticles ranged from 20 to 90 nm. The results show that adverse effects on cell function, as evidenced by reduced metabolic activity measured by the MTT assay and increased membrane permeability observed using the live/dead stain, can be correlated with surface area of the silica. Cisplatin-functionalized silica nanoparticles with the highest surface area incited the greatest response, which was almost equivalent to that induced by free cisplatin. Moreover, if verified by further studies, would indicate that cisplatin was attached to silica nanoparticles might prove to be useful in site-specific drug delivery.Electronic supplementary materialThe online version of this article (doi:10.1007/s12645-013-0043-6) contains supplementary material, which is available to authorized users.
Highlights
Worldwide, deaths: an estimated 39,920 breast cancer deaths (39,510 women, 410 men) are expected in 2012
Effects on metabolic activity as measured via the methyl-thiazol tetrazolium salts (MTT) assay, and membrane permeability observed by fluorescence microscopy using the DAPI/JC-1 live/dead stain, we demonstrated that these silica-cisplatin prodrug conjugate NPs had wellcontrolled drug loading yield, excellent acid-responsive drug release characteristics, and potent cytotoxicity against breast cancer
In a study of silica, the silanol surface concentration was found to vary only slightly with surface area: 2.1 groups/nm2 for Triton X-100, which is made at high flame temperatures to facilitate larger primary particle diameters, versus 2.4–2.5 groups/nm2 reported for Aerosil samples (Bhowmick et al 2010)
Summary
Deaths: an estimated 39,920 breast cancer deaths (39,510 women, 410 men) are expected in 2012. The testable hypothesis is that nontoxic nanoparticles with a surface-attached toxic molecule would adversely affect cell function, defined here by reduced metabolic activity and increased membrane permeability. These adverse effects are expected to increase with increasing surface area. Effects on metabolic activity as measured via the MTT assay, and membrane permeability observed by fluorescence microscopy using the DAPI/JC-1 live/dead stain, we demonstrated that these silica-cisplatin prodrug conjugate NPs had wellcontrolled drug loading yield, excellent acid-responsive drug release characteristics, and potent cytotoxicity against breast cancer
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