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Cisplatin-Loaded Porous Si Microparticles Capped by Electroless Deposition of Platinum

Authors

  • Jennifer S. Park,

    1. Department of Bioengineering, University of California – San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0358, USA
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  • Joseph M. Kinsella,

    1. Department of Chemistry and Biochemistry, University of California – San Diego, 9500 Gilman Drive, La Jolla, CA 92093–0358, USA
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  • Danielle D. Jandial,

    1. Division of Gynecologic Oncology, University of California Irvine Medical Center, 101 The City Drive, Building 56 Room 206, Orange, CA 92868, USA
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  • Stephen B. Howell,

    1. John and Rebecca Moores Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093, USA
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  • Michael J. Sailor

    Corresponding author
    1. Department of Bioengineering and Department of Chemistry and Biochemistry, University of California – San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA
    • Department of Bioengineering and Department of Chemistry and Biochemistry, University of California – San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
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Abstract

The loading and release of the anti-cancer drug platinum cis-dichlorodiamine (cisplatin) from mesoporous silicon (pSi) microparticles is studied. The pSi microparticles are modified with 1-dodecene or with 1,12-undecylenic acid by hydrosilylation, and each modified pSi material acts as a reducing agent, forming a deposit of Pt on its surface that nucleates further deposition, capping the mesoporous structure and trapping free (unreduced) cisplatin within. Slow oxidation and hydrolytic dissolution of the Si/SiO2 matrix in buffer solution or in culture medium leads to the release of drugs from the microparticles. The drug-loaded particles show significantly greater toxicity toward human ovarian cancer cells (in vitro), relative to an equivalent quantity of free cisplatin. This result is consistent with the mechanism of drug release, which generates locally high concentrations of the drug in the vicinity of the degrading particles. Control assays with pSi particles loaded in a similar manner with the therapeutically inactive trans isomer of the platinum drug, and with pSi particles containing no drug, result in low cellular toxicity. A hydrophobic pro-drug, cis,trans,cis-[Pt(NH3)2(O2C(CH2)8CH3)2Cl2], is loaded into the pSi films from chloroform without concomitant reduction of the pSi carrier.

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