Non-viral Gene Therapy - Intracellular Delivery: Fundamentals and Applications - page 664

into the intracellular or in vivo transportation and/or distribution, and valuable
information on the spatial and temporal interactions of delivery carriers with cells
and tissues as well as their intracellular interactions. In addition, multifunctional
nanoparticles have also been employed to implement the simultaneous gene delivery,
drug delivery and imaging (Qi and Gao 2008b ; Nehilla et al. 2008 ; Liong et al. 2008 ;
Ghosh et al. 2008 ; Al-Jamal et al. 2008 ; Farokhzad and Langer 2009 ).

6.1 Multifunctional Magnetic Nanoparticles

Magnetic nanoparticles are 10-20 nm sized spherical nanocrystals with a Fe 2+ and
Fe 3+ core surrounded by dextran or PEG chains (Lu et al. 2007 ). In addition to
active targeting triggering using external magnetic field, their special magnetic
properties make them excellent agents to label biomolecules in bioassays, as well
as magnetic resonance imaging (MRI) contrast agents to trace the in vivo biodistri-
bution or accumulation of delivery vehicles by high-resolution MRI.
Recently, Moore and coworkers reported the development of dual-purpose
probes for in vivo transfer of siRNA and the simultaneous imaging of its accumula-
tion in tumors by MRI and near-infrared in vivo optical imaging (NIRF) (Medarova
et al. 2007 ). These nanoplatforms comprised magnetic nanoparticles labeled with a
near-infrared dye (cyanine dye Cy5.5) and covalently linked to siRNA molecules.
Additionally, these nanoparticles were peripherally decorated with a membrane
translocation peptide (myristoylated polyarginine peptide) for intracellular delivery.
The tumor could be imaged via T2 MR and NIR fluorescent imaging, after the
intravenous injection of the nanoparticles into nude mice bearing subcutaneous
human colorectal carcinoma tumors. Gene silencing was observed only when the
multimodal nanoparticles-containing siRNA were administered. These studies rep-
resent the first step towards the advancement of simultaneous delivery and detection
of siRNA-based therapeutic agents in vivo , essential for cancer therapeutic product
development and optimization. Park and Cheon et al. have developed “all-in-one”
nanoparticle probes for simultaneous siRNA delivery and multimodal imaging (Lee
et al. 2009 ). To achieve this purpose, manganese-doped magnetism-engineered iron
oxide (MnMEIO) nanoparticles of 15 nm in size coated with bovine serum albumin
(BSA) were used as the core material, onto which RGD functionalized PEG and
Cy5-dye-labeled sRNA were conjugated via the disulfide linkage. Besides the intra-
cellular delivery of therapeutic siRNA, these multifunctional nanoprobes enable
highly accurate imaging by both MRI and fluorescence imaging.

6.2 Quantum Dots as Multifunctional Vectors

Quantum dots (QDs) are colloidal fluorescent semiconductor nanocrystals of
2-10 nm. The central core of QDs composes of element combinations from groups
II-VI of the periodic table (CdSe, CdTe, CdS, PbSe, ZnS and ZnSe) or III-V