Introduction: IR820 is a near-infrared probe with potential applications in optical imaging and hyperthermia. Its chlorosubstituted cyclohexene makes it amenable to forming conjugates as multifunctional probes. We prepared a novel covalent IR820/PEG-diamine (IRPDcov) nanoconjugate.
Methods: IRPDcov was prepared using IR820 and 6kDa PEG-diamine, characterized by SEM, H-NMR,
spectrophotometry, and spectrofluorometry; and studied in vitro and in vivo. Mice (n=36) were used to explore the
biodistribution of IRPDcov compared to IR820 and indocyanine green (ICG) after i.v. injection of a 0.24 mg/kg dose of
dye, with plasma samples collected at 15-30-60 minutes and 24 hours. The plasma concentrations were fit to a
biexponential curve following a two compartment model. Organ samples were collected after 24 hours.
Results and Discussion: IRPDcov retained the ability to fluoresce for in vivo optical imaging and also to generate heat, and was significantly more stable than IR820 in aqueous solution over a period of 72 hours. IRPDcov and IR820
demonstrated significantly longer (p<0.05) plasma half-lives, elimination half-lives, and area-under-the-curve values
compared to ICG. This could pose an advantage in therapeutic probe applications such as hyperthermia or drug delivery. Both IR820 and IRPDcov showed a very strong signal in the liver and lower-intensity signal in the kidneys 24 hours after injection, whereas the predominant signal for ICG was weak and located in the intestines, demonstrating a much more rapid GI elimination. IR820 showed signal in the lungs, which was not present in IRPDcov subjects indicating that IRPDcov may have been able to escape detection by alveolar macrophages.
Introduction: Recent research has focused on developing new biomaterials for delivery of imaging agents and drugs. In our study, we report a new biocompatible and biodegradable polymer, termed poly(glycerol-co-malic-dodecanoate) (PGMD), which was then used for synthesis of nanoparticles (NPs) and loading of NIR dyes.
Methods: The PGMD polymer was synthesized via thermal condensation method and was characterized by FTIR. The NPs were synthesized via o/w single emulsion technique. IR820 was chosen as the NIR dye. The loading efficiency of IR820 in PGMD NPs was measured by spectrophotometer. The release of IR820 was estimated with a spectrofluorometer in different pH phosphate buffered saline. The cytotoxicity of NPs was estimated through a
Sulforhodamine B colorimetric assay. A biodistribution and pharmacokinetics study of the NPs versus free IR820 was
performed in a murine model (n=12) after i.v. injection. Plasma samples were collected at time points 15-30-60 minutes
and 24 hours. Organ samples were also collected and measured at the 24-hour time point.
Results and Discussion:
Void PGMD NPs and IR820-PGMD NPs had mean sizes around 90 nm and 110 nm, respectively. FTIR showed that
polyester bonds were forming in the PGMD polymer. The release of IR820 was increased in acidic buffer (pH=5.0) as
compared to neutral buffer (pH=7.4), indicating that the release of IR820 is controllable. Cellular uptake studies showed comparable fluorescence of IR820-PGMD NPs to free IR820 (5 μM) after 24-hour exposure. IR820-PGMD NPs
induced significant cancer cell killing after laser exposure due to the photothermal effect of the dye. In vivo studies
showed that the IR820 in NPs formulation has a longer plasma half-life than free IR820, providing longer imaging
collection times for cancer diagnostics, and potentially widening the window for hyperthermia applications.
Conclusion:
We expect that ease of synthesis and good biocompatibility make PGMD a good candidate for numerous imaging agent and drug delivery applications. The IR820-PGMD NPs have the ability to be used for both imaging and hyperthermia purposes.
We previously reported on the synergistic effects of hyperthermia and chemotherapy using doxorubicin
(DOX) and Indocyanine Green (ICG). In a previous study we also explored the potential use of simultaneous entrapment
of optical/imaging and chemotherapeutic agents into PLGA nanoparticles. The aim of the present study is to further
decorate their surface with tumor specific monoclonal antibodies in order to achieve simultaneous therapy and diagnosis
in a targeted manner. Thus, ICG was selected as an imaging agent due to its wide clinical applications and since it can
also serve as hyperthermia agent. DOX was selected as the chemotherapeutic agent since it is used clinically for a large
spectrum of tumors.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.