Design and Development of Theranostic Nanomedicines - Nanotechnology for Biomedical Imaging and Diagnostics - page 438

modalities (Mri and nirF) showed high specificity for the growing tumors. Though
imaging was successfully used to visualize tumor growth and nanoemulsion distribu-
tion, confirmation on drug effects was obtained from histological data and molecular
analysis of excised tissues [137].
15.4 selecteD polymeric nanosystems
15.4.1 Dendrimers
Dendrimers are perfectly hyperbranched macromolecules with a large number of sur-
face functional groups that define their properties and activity [138]. The architecture
of dendrimers consists of a core surrounded by generations of covalently linked
branched interiors [139]. This creates layered structure that grows as the dendrimer
generation increases. Therefore, unlike most other types of nanoparticles, dendrimers
have precisely controlled size, shape, and surface chemistry [140]. These unique
properties allow dendrimers to be developed with high structural monodispersity,
desired plasma circulation time, and biodistribution properties, as well as control over
drug release. The abundant surface functional groups make dendrimers platforms for
attachment of specific targeting groups, surface modifiers, imaging agents, and
therapeutic drugs. These tunable properties, together with the precisely controlled
structure, render dendrimers attractive theranostic agents. The most commonly
studied dendrimeric structures are the polyamidoamine (paMaM, Fig. 15.7) and
polypropylenimine (ppi) dendrimers. Unlike ionp, CnTs, and gnps, dendrimers
do not possess any intrinsic signaling moieties. however, they can be used in a range
of imaging modalities through their abundant surface functional groups. For example,
nir fluorescent dyes can be conjugated to dendrimers for optical imaging. it is also
possible to use dendrimer in peT, speCT, or Mri by attaching chelated 64 Cu 2+ ,
111 in 3+ , or gd 3+ to the dendrimer surface. The emerging interest in multimodal imaging
has also been met using dendrimers as the platforms. For instance, a bimodal Mr/
nir fluorescence contrast agent was synthesized by attaching DTpa chelated gd 3+
and Cy5.5 dye to the surface of a generation 6 (g6) paMaM dendrimer [142].
Drug molecules can be either encapsulated within the nanostructure or covalently
conjugated to the surface of dendrimers. noncovalent encapsulation is usually asso-
ciated with hydrogen bonding or hydrophobic or ionic interactions [140]. Covalent
conjugation between anticancer drugs and dendrimer surface is typically through a
labile linker, such as a disulfide, peptide, or ester linker, that is tailored to release the
drug in a controlled fashion. although noncovalent encapsulation has the advantage
of easy drug loading without synthesis and drug regulatory issues, it is challenged by
the burst release of drug molecules in plasma, which often leads to very limited
therapeutic benefit compared to free drug molecules [140]. several drugs have been
loaded into dendrimers through noncovalent encapsulation, such as MTX in a g2
polyester copolyether dendrimer [143], DoX in a g3 paMaM dendrimer [144],
pTX in a g5 polyglycerol dendrimer [145], and 5-fluorouracil (5-FU) in paMaM
dendrimers [146].