q 2006 by Taylor & Francis Group, LLC - Developers

Introduction and Rationale for Nanotechnology in Cancer Therapy 7
Another class of nanovectors described in the following chapters is dendrimers, which are self
assembling synthetic polymers possessing tunable nanoscale dimensions that assume conformations
that are dependent upon the microenvironment. The development of polymeric micelles
preceded the development of dendrimers. However, due to the characteristics of dendrimers as
“perfectly branched monodispersed macromolecules,” 39 this class of nanovectors may be suitable
as exquisitely sensitive carriers for defined release of anti-tumor agents, as well as very useful for
targeted delivery of such molecules as contrast agents for tumor imaging.
Dendritic nanocarriers have been evaluated for their capability to serve as nanovectors for
delivery of drugs and for plasmid DNA, suggesting that dendrimer nanovectors may be useful
for gene therapy. 40 Like liposomes, dendrimers can also be modified by PEGylation 41 to increase
their bioavailability and half-life in the circulation. Dendrimers have been shown to be suitable for
enhancing the solubility of drugs, and to have suitable profiles for controlled delivery as well as
selective delivery of drugs such as flurbiprofen that are active within a local site of inflammation. 42
Although dendrimers that have been evaluated for potential utility in cancer therapeutics have
primarily been composed of polyamidoamine (PAMAM), there are also gold/dendrimer nanocomposites
43 and silver/dendrimer nanocomposite materials 44 that have been developed and are
currently being evaluated for their comparative chemical and biological characteristics with
potential utility as biomarkers, as well as for use in cancer therapeutics, tumor imaging, and
radiotherapy.
The varied nature of nanovectors covered in Nanotechnology for Cancer Therapy is illustrated
by such novel classes of nanocarriers as DQAsomes, which are mitochondrial-targeted nanovectors
capable of delivery of anti-cancer drugs as well as carriers of gene therapy directed against this
organelle. 44,45 The development of this nanovector delivery approach is based on the relatively
recent realization that a number of genetic disorders associated with defects in oxidative metabolism
are associated with genetic defects in mitochondrial DNA, with a significant lack of available
therapies. While the majority of nanovectors target tumors and/or tumor-associated vasculature, the
DQAsomes are composed of derivatives of the self-assembling mitochondriotropic bola-amphiphile
dequalinium chloride, which forms cationic vesicles which can bind and transport DNA to
mitochondria in living mammalian cells. 44
Another approach using selective targeting of more classically used characteristics of cancer
cells includes the development of lipoprotein nanoparticles as delivery vehicles for anti-cancer
therapy. 46 These high density lipoprotein (rHDL) nanoparticles are composed of phosphatidylcholine,
apolipoprotein A-1, cholesterol, and cholesteryl esters with encapsulated paclitaxel.
They were shown to be useful as a nanovector for anti-tumor drug delivery based on the ability
of cancer cells to selectively acquire HDL, while the use of these nanovectors decreased the side
effects normally observed with this type of anti-tumor therapy.
Given the wide variety of nanovectors and nanoplatforms, Nanotechnology for Cancer Therapy
cannot possibly cover each nanoscale application that has potential for use in anti-tumor therapy
and tumor imaging. One nanoplatform that should be mentioned is the so-called “quantum dots”
(Q-dots) that have recently received wide attention. Although cadmium and selenium crystalline
nanovectors were first used over two decades ago, Q-dots have recently received attention for their
utility as tunable multicolor nanoparticles that can be used for in vivo tumor imaging in animal
models of cancer as well as for multiplex detection of mRNAs and proteins. Although the current
composition of the Q-dots nanovectors prohibits their clinical use for cancer therapy, there is
significant promise for the potential for development of biocompatible nanovectors which are
tunable to wavelengths useful for tumor imaging. They may provide the ability to selectively
target tumors as well as serve as multifunctional nanovector devices for cancer therapy,
imaging, diagnostics, and monitoring of response to anti-tumor therapy.
Although the development of nanoplatforms for cancer therapeutics is a critical component to
the successful use of nanovectors for anti-tumor therapy and tumor imaging, there are other necessary
components for nanoplatforms to gain clinical acceptance. One such parameter is the necessary
q 2006 by Taylor & Francis Group, LLC