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Volume 4
Nano Research & Applications
ISSN: 2471-9838
Page 47
JOINT EVENT
August 16-18, 2018 | Dublin, Ireland
&
12
th
Edition of International Conference on
Nanopharmaceutics and Advanced Drug Delivery
25
th
Nano Congress for
Future Advancements
Nano Congress 2018
&
Nano Drug Delivery 2018
August 16-18, 2018
Nano particle targeting assessed by novel photo acoustic and pet imaging: Internal normalization by
multi spectral imaging
Robert K Prud'homme
1,2
, Leon Z Wang
1
, Hoang D Lu
1
, Tristan L Lim
1
, Brian K Wilson
1
and
Andrew Heinmiller
1,2
1
Princeton University, USA
2
FUJIFILM VisualSonics Inc., Canada
T
here is an increased demand for fast and inexpensive methods to determine cancer phenotypes and morphologies. Current
in vivo
diagnostic imaging modalities utilizing X-ray CT, MRI, and PET scans are limited to black-white images that
cannot be used to differentiate multiple disease marker contrast agents at a time. In addition, targeting studies in which each
nanoparticle (NP) type must be individually administered to an animal result in large numbers of animals that must be used in
a study to obtain reliable statistics. This requires both significant time and expense. Photoacoustic (PA) imaging, a hybrid light
and sounds imaging technique, has shown to be a safe and inexpensive diagnostic technique with high spatial resolution in
3D. Traditional PA contrast agents, however, tend to have broad absorption peaks in the NIR range which renders it difficult to
simultaneously image more than one signal at a time in deep tissue. Here we present the formulation of a series of PA active NPs
with sharp and separable absorbance profiles in the NIR range for simultaneous multiplexed imaging. PA dyes are encapsulated
inside NPs using the controlled self-assembly mechanism, Flash nanoprecipitation (FNP). Four new contrast agents, with
sharp absorbance maxima between 600-900 nm, were created by encapsulating a variety of phthalocyanine derivatives. We
were able to simultaneously detect the concentrations of contrast agents mixed together with >95% deconvolution efficacy.
As a proof of concept, we co-injected RGD modified NPs and non-modified NPs with different labeling agents and tracked
NP biodistributions for both particles simultaneously. Using this technology, we accessed the effect of NP ligand modification
on both targeting efficacy onto the tumors and off targeting accumulation in the liver using a single animal model. Over
modification of the NPs resulted in rapid liver clearance and poor accumulation in the tumor; at low modifications, the tumor
to liver accumulation ratio is 9.9±4.2, while at high RGD modifications the tumor to liver accumulation ratio is 52±22. The
ability to simultaneously inject control particles and targeted particles, and to follow their fate greatly enhances the ability to
design targeted nanoparticles. The same phthalocyanine dyes effectively chelate PET active cations to enable whole animal PET
imaging. The FNP technology enables the production of both NPs that enable PAI and PET imaging.
Recent Publications
1. Lu H D et al. (2017) Assembly of macrocycle dye derivatives into particles for fluorescence and photoacoustic
applications. ACS Combinatorial Science. 19(6):397-406.
2. Lu H D et al. (2015) Modulating vibrio cholerae quorum-sensing-controlled communication using autoinducer-
loaded nanoparticles. Nano Letters. 5(4):2235-2241.
3. Lu HD et al. (2017) Copper loading of pre-formed nanoparticles for PET-imaging applications. ACS AppliedMaterials
& Interfaces. 10(4):3191-3199.
4. Lu H D et al. (2017) Real-time and multiplexed photoacoustic imaging of internally normalized mixed-targeted
nanoparticles. ACS Biomaterials Science & Engineering. 3(3):443-451.
5. Lu HD et al. (2017) Nanoparticle targeting of grampositive and gram-negative bacteria for magnetic-based separations
of bacterial pathogens. Applied Nanoscience. 7(3-4):83-93.
Biography
Robert K Prud'homme is a Professor in the Department of Chemical and Biological Engineering at Princeton University, USA. He is the Founding Director of the
Program in Engineering Biology. His research program focusses on polymer self-assembly applied to drug delivery. The development of Flash Nanoprecipitation
(FNP) in his laboratory enabled the encapsulation of poorly soluble drug compounds and oligonucleotides for therapy directed towards cancer, TB, and injections.
FNP is a scalable and continuous process that is enables integrated processing and spray drying for low cost oral and aerosol formulations. Under sponsorship by
the Bill and Melinda Gates Foundation, the process is being adopted to formulate new compounds coming from TBA, MMV, and DNDi.
Prudhomm@princeton.eduRobert K Prud'homme et al., Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C3-014