Near-infrared fluorescing IR820-chitosan conjugate for multifunctional cancer theranostic applications.
This study reports the preparation and characterization of IR820-chitosan conjugates that have potential multifunctional imaging-hyperthermia applications in cancer. The conjugates were formulated by covalentcouplingofchitosan to a carboxyl derivatized IR820, and studied for optical imaging and hyperthermia applications. IR820-chitosan conjugates were able to generate heat upon exposure to 808nm laser and produce hyperthermic cell growth inhibition in cancer cell lines MES-SA, SKOV-3 and Dx5. The level of cell growth inhibition caused by hyperthermia was significantly higher for IR820-chitosan compared to IR820 in MES-SA and Dx5 cells. Fluorescent microscope images of these cancer cell lines after 3-h exposure to 5μM IR820-chitosan showed that the conjugates can be used for in vitro near-infrared imaging. In an in vivo rat model, the conjugates accumulated in the liver after i.v. injection and were excreted through the gastrointestinal tract, demonstrating a different biodistribution when compared to the free dye. The accumulation of these conjugates in bile with subsequent gastrointestinal excretion allows for potential applications as gastrointestinal contrast agents and delivery vehicles. This formulation can potentially be used in multifunctional cancer theranostics.
Florida International University, Biomedical Engineering Department, 10555 W. Flagler St., EC 2613, Miami, FL 33174, USA.
Supriya
S
Srinivasan
Romila
R
Manchanda
Alicia
A
Fernandez-Fernandez
Tingjun
T
Lei
Anthony J
AJ
McGoron
D000042:Absorption; D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D005243:Feces; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007208:Indocyanine Green / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D007259:Infrared Rays; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects; D008856:Microscopy, Fluorescence / Q000379:methods*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D017550:Spectroscopy, Fourier Transform Infrared
D003287:Contrast Media; D005456:Fluorescent Dyes; C541053:IR 820; D048271:Chitosan; D007208:Indocyanine Green