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Nanoscale Dendrimer-Platinum Conjugates as Multivalent Antitumor Drugs

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Inorganic and Organometallic Macromolecules

Organoplatinum anti-tumor compounds function as broad spectrum, highly effective anticancer drugs. However, the toxicity of these compounds has plagued their use from the outset. In an attempt to enhance the delivery and mitigate the side-effects associated with the use of these drugs, a wide variety of polymer-drug conjugates have been prepared and evaluated for antitumor activity. The advent of dendrimers, and polymers with well-defined size, shape, and surface functionality, has provided the opportunity for the development of organoplatinum antitumor agents of enhanced activity and diminished toxicity. A generation 4.5 PAMAM dendrimer (carboxylate surface) has been treated with diaquo(1,2-diaminocyclohexane)platinum(II) to generate a well-defined dendrimer-platinum conjugate containing forty (1,2-diaminocyclohexane)platinum(II) units coordinated to the dendrimer surface via carboxylate groups. This adduct is well-behaved, water-soluble, contains a high loading of platinum, and displays sustained release of active platinum species over a 24 hour period under physiological conditions. It seems to offer great potential as a new nanoscale multivalent organoplatinum antitumor agent.

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Authors and Affiliations

  1. Center for Applications in Polymer Science and Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859, USA

    Bob A. Howell

  2. Center for Applications in Polymer Science, Central Michigan University, Mount Pleasant, MI 48859, USA

    Daming Fan & Leela Rakesh

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Editors and Affiliations

  1. The University of British Columbia, Okanagan, 3333 University Way, V1V 1V7, Kelowna, British Columbia, Canada

    Alaa S. Abd-El-Aziz

  2. Department of Chemistry & Biochemistry, Florida Atlantic University, 777 Glades Rd., 33431, Boca Raton, Florida, USA

    Charles E. Carraher Jr.

  3. Department of Chemistry, Mississippi State University, 39762, Mississippi State, Mississippi, USA

    Charles U. Pittman Jr.

  4. Department of Chemistry, University of Richmond, 28 Westhampton Way, 23173, Richmond, Virginia, USA

    Martel Zeldin

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Howell, B.A., Fan, D., Rakesh, L. (2008). Nanoscale Dendrimer-Platinum Conjugates as Multivalent Antitumor Drugs. In: Abd-El-Aziz, A.S., Carraher, C.E., Pittman, C.U., Zeldin, M. (eds) Inorganic and Organometallic Macromolecules. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72947-3_11

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