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Biochemical Society Transactions (2007) 35, (61–67) (Printed in Great Britain)

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Biochemical Society Focused Meetings

Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging

D.A. Tomalia*†¹, L.A. Reyna* and S. Svenson*

*Dendritic Nanotechnologies Inc., 2625 Denison Drive, Mt. Pleasant, MI 48858, U.S.A., and †Department of Chemistry, Central Michigan University, Mt. Pleasant, MI 48859, U.S.A.

Key words: dendrimer, diagnostic imaging, nanocontainer, nanomedicine, nanoscaffolding, targeted delivery.

Abbreviations used: EPR, enhanced permeability retention; MRI, magnetic resonance imaging; PAMAM, polyamidoamine; PEG, poly(ethylene glycol); P-gp, P-glycoprotein.

¹To whom correspondence should be addressed (email tomalia@dnanotech.com).

Abstract

Dendrimers are routinely synthesized as tuneable nanostructures that may be designed and regulated as a function of their size, shape, surface chemistry and interior void space. They are obtained with structural control approaching that of traditional biomacromolecules such as DNA/RNA or proteins and are distinguished by their precise nanoscale scaffolding and nanocontainer properties. As such, these important properties are expected to play an important role in the emerging field of nanomedicine. This review will describe progress on the use of these features for both targeted diagnostic imaging and drug-delivery applications. Recent efforts have focused on the synthesis and pre-clinical evaluation of a multipurpose STARBURST® PAMAM (polyamidoamine) dendrimer prototype that exhibits properties suitable for use as: (i) targeted, diagnostic MRI (magnetic resonance imaging)/NIR (near-IR) contrast agents, (ii) and/or for controlled delivery of cancer therapies. Special emphasis will be placed on the lead candidate, namely [core: 1,4-diaminobutane; G (generation)=4.5], [dendri-PAMAM(CO₂Na)₆₄]. This dendritic nanostructure (i.e. ~5.0 nm diameter) was selected on the basis of a very favourable biocompatibility profile [The Nanotechnology Characterization Laboratory (NCL), an affiliate of the National Cancer Institute (NCI), has completed extensive in vitro studies on the lead compound and have found it to be very benign, non-immunogenic and highly biocompatible], the expectation that it will exhibit desirable mammalian kidney excretion properties and demonstrated targeting features.

Received 22 August 2006

© 2007 Biochemical Society