Design and Development of Theranostic Nanomedicines - Nanotechnology for Biomedical Imaging and Diagnostics - page 425

and lysozymes after the drug nanoparticle conjugate was internalized in cancer cells
[15]. For drug molecules without appropriate functional groups, they can be loaded
into certain porous iron oxide nanostructures. For instance, commonly used cancer
drugs, doxorubicin (DoX) and cisplatin, were found to be absorbed into hollow
ionps and released under physiologic conditions in a sustained manner [16, 17].
although passive targeting mediated by enhanced permeability and retention
(epr) effect is commonly used to deliver ionps to the target tumor region [16, 18],
it is more desirable to introduce targeting moieties, such as antibodies, peptides, and
ligands, to the surface of ionps. Through specific interactions between the targeting
moieties on ionps and corresponding receptors on cancer cell membranes, ionps
can accumulate on the cell membranes or be internalized through receptor-mediated
endocytosis, therefore enhancing imaging contrast and therapeutic efficacy. The suc-
cess of targeted delivery of ionps to cancer cells largely depends on the size and
surface engineering. it is critical that ionps have circulation time long enough to
reach the target sites. ionps with sizes smaller than 10 nm will be filtered out of the
blood rather quickly because the basal lamina of the kidneys has pores of approxi-
mately 10nm [5]. ionps larger than 100nm are prone to be uptaken by the
reticuloendothelial system (res) [11]. Therefore, ionps with sizes between 10 and
100nm are generally considered appropriate for targeted delivery. other than the
size, the other key consideration is surface engineering. it is important to graft ionp
surface to achieve desired functionality, hydrophilicity, biostability, and specificity.
a common approach to reduce nonspecific adsorption and enhance stability of
ionps in plasma is to introduce peg to the surface. some permeating molecules,
such as amphipathic peptides and chitosan (a polysaccharide polymer), have been
used to facilitate ionps penetrate the blood-brain barrier (BBB) [19-21].
The classical synthetic method of ionps involves coprecipitation of Fe(ii) and
Fe(iii) with polymer under basic aqueous condition. Tangled with the nanocrystals,
the polymer can protect the particles from aggregation and overgrowth [11]. a
well-known example of ionps synthesized from coprecipitation is cross-linked iron
oxide (Clio) nanoparticles, which use aminated or carboxylated dextran as the
coating polymer [22, 23]. The functional groups (primary amino or carboxyl) dis-
tributed throughout the nanostructure allow for bioconjugation to various signaling,
targeting, and therapeutic molecules.
Coprecipitation is simple and scalable; however, this method is challenged by
limited control over the size, shape, and composition of ionps. To address this
limitation, the thermal decomposition method was later developed. This method
involves high temperature reaction in organic solution and can produce highly
monodispersed ionps [24]. The major disadvantage is that the resulting ionps are
usually not soluble in water, thus limiting the extent of biological applications. To
introduce hydrophilicity, biocompatibility, and functionality to ionps developed
from thermal decomposition method, surface modification is necessary. several
such modification techniques have been developed, such as ligand exchange [25]
and ligand addition [26].
The superior magnetic properties and versatile surface chemistry have rendered
ionps a promising platform for in vivo therapeutic studies. For example, Yu et al .