Biomedical Engineering Reference
In-Depth Information
mediated endocytosis of conjugates and subsequent silencing effects on the
target gene through RNA interference. CdSe particles may leak cytotoxic
cadmium ions after long-term exposure to ultraviolet light, whereas CdTe
particles produce reactive oxygen species as a result of the loss of their pro-
tective coating after longterm circulation.
5.12 Dendrimers
A dendrimer is generally defined as a macromolecule which is characterized
by its highly branched 3D structure, which provides a high degree of sur-
face functionality and versatily (Figure 2-2) [176]. The generation number
and the chemical composition of the core, branches, and surface functional
groups, determine the size, shape, and reactivity of dendrimers. Dendrimers
have attracted attention as possible drug carriers because of their unique
properties, namely their well defined three-dimensional structure, the avail-
ability of many functional surface groups, their low polydispersity, and
their ability to mimic. Dendrimers can function as drug carriers either by
encapsulating drugs within the dendritic structure, or by inter-acting with
drugs at their terminal functional groups via electrostatic or covalent bonds
(prodrug) [177]. Dendrimers have been studied extensively for targeting
and delivery of therapeutic agents for cancer and of contrast agents for mag-
netic resonance imaging. The avidimers are dendrimers targeted to tumor
vasculature using a methotrexatepolyamidoamine (PAMAM) bioconjugate
platform functionalized with small targeting ligands [178]. The authors dem-
onstrated in vitro, that drug-free dendrimer conjugates were not cytotoxic,
and that drug-loaded dendrimer conjugates had no effect on folate receptor-
negative cells. Polyanionic PAMAM dendrimers showed rapid serosal
transfer rates in crossing an adult rat intestine in vitro, and had low tis-
sue deposition. The transport of PAMAM and surface-modified PAMAM
across cell monolayer follows endocytosis-mediated cellular internalization.
However, non-biodegradable dendrimers may potentially accumulate in lys-
osomes depending on their frequency and dose of administration. Various
studies report that PEG-modified dendrimers show reduction of cytotox-
icity and immunogenicity, high exocytosis rate and low accumulation in
endothelial cells, with excellent solubility and a favorable pharmacokinetic
[179]. Amine-terminated polyamidoamine (PAMAM) dendrimers appear
to be an ideal class of building blocks for developing multifunctional gene
vectors. Angiopep is a high brain penetration peptide, which targets to the
low-density lipoprotein receptor-related protein-1. Ke et al. [180] coupled
angiopep to PEGylated PAMAM dendrimer G5.0 via the distal end of PEG,
and used it to deliver pEGFP-N2 plasmid to the brain both in vitro and in
vivo. The plasmid DNA covalently labeled with fluorescent dye, ethidium
monoazide bromide (EMA), was detected in the brain of the mice treated with
the PAMAMPEG-Angiopep/DNA. Multimodal dendrimer-conjugated
magnetofluorescent nanoworms, called dendriworms, were developed recently
