Multimodal imaging systems are in high demand for preclinical research, experimental medicine, and clinical practice. Combinations of photoacoustic technology with other modalities including fluorescence, ultrasound, MRI, OCT have been already applied in feasibility studies. Nevertheless, only the combination of photoacoustics with ultrasound in a single setup is commercially available now. A combination of photoacoustics and fluorescence is another compelling approach because those two modalities naturally complement each other. Here, we presented a bimodal contrast agent based on the indocyanine green dye (ICG) as a single signalling compound embedded in the biocompatible and biodegradable polymer shell. We demonstrate its remarkable characteristics by imaging using a commercial photoacoustic/fluorescence tomography system (TriTom, PhotoSound Technologies). It was shown that photoacoustic signal of the particles depends on the amount of dye loaded into the shell, while fluorescence signal depends on the total amount of dye per particle. For the first time to our knowledge, a commercial bimodal photoacoustic/fluorescence setup was used for characterization of ICG doped polymer particles. Additionally, we conducted cell toxicity studies for these particles as well as studied biodistribution over time in vivo and ex vivo using fluorescent imaging. The obtained results suggest a potential for the application of biocompatible and biodegradable bimodal contrast agents as well as the integrated photoacoustic/fluorescence imaging system for preclinical and clinical studies.
Nanocomposite
capsules containing magnetite nanoparticles (MNPs)
are promising multifunctional drug delivery systems for various biomedical
applications. The presence of MNPs allows one to visualize these capsules
via magnetic resonance imaging (MRI) and optoacoustic (photoacoustic)
imaging. Moreover, we can ensure precise navigation and remote release
via a magnetic field gradient and alternating magnetic fields, respectively.
Magnetic dipole–dipole interaction between single capsules
is important when a magnetic field is applied, and it is determined
by a magnetic moment of each individual capsule. However, there is
a lack of experimental data on the magnetic moment of a single capsule.
Physical properties of capsules vary due to the change in the volume
fraction of MNPs, as well as the capsule shell architecture. Therefore,
two types of submicron capsules with different amounts of MNPs were
synthesized. The first type of capsules was prepared by freezing-induced
loading and layer-by-layer (LbL) assembly. The amount of MNPs varied
by the number of freezing-induced loading cycles: two, four, and six.
The second type of capsules is a nanocomposite shell formed using
the LbL assembly of the oppositely charged polyelectrolytes and MNPs.
Structural properties of both types of submicron capsules and MNPs
were studied using transmission electron microscopy. Magnetic moments
of nanocomposite shells placed in an external magnetic field were
directly measured by optical tweezers and calculated based on vibrating-sample
magnetometer measurements of the water suspension of nanocomposite
shells. The magnetic moment of an individual shell depends on the
amount of MNPs and increases as the number of MNPs per shell grows.
Magnetic coupling parameters and the specific absorption rate were
calculated. The obtained results can be applied while preparing drug
carrier systems sensitive to alternating magnetic fields and navigated
by gradient magnetic fields. They can also be taken into account in
device development for navigating drug delivery systems and for the
treatment based on alternating magnetic field-induced hyperthermia.
We present a targeted drug delivery
system for therapy and diagnostics
that is based on a combination of contrasting, cytotoxic, and cancer-cell-targeting
properties of multifunctional carriers. The system uses multilayered
polymer microcapsules loaded with magnetite and doxorubicin. Loading
of magnetite nanoparticles into the polymer shell by freezing-induced
loading (FIL) allowed the loading efficiency to be increased 5-fold,
compared with the widely used layer-by-layer (LBL) assembly. FIL also
improved the photoacoustic signal and particle mobility in a magnetic
field gradient, a result unachievable by the LBL alone. For targeted
delivery of the carriers to cancer cells, the carrier surface was
modified with a designed ankyrin repeat protein (DARPin) directed
toward the epithelial cell adhesion molecule (EpCAM). Flow cytometry
measurements showed that the DARPin-coated capsules specifically interacted
with the surface of EpCAM-overexpressing human cancer cells such as
MCF7. In vivo and ex vivo biodistribution
studies in FvB mice showed that the carrier surface modification with
DARPin changed the biodistribution of the capsules toward epithelial
cells. In particular, the capsules accumulated substantially in the
lungsa result that can be effectively used in targeted lung
cancer therapy. The results of this work may aid in the further development
of the “magic bullet” concept and may bring the quality
of personalized medicine to another level.
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