Original ArticleTargeted near-IR hybrid magnetic nanoparticles for in vivo cancer therapy and imaging
Graphical Abstract
Gold hybrid nanoparticles (HNPs) targeted with A33 single-chain antibody showed efficacious photothermal therapy ablative capability after tumor trophic accumulation. Histological assessment of treated tumor showed over 65% necrosis on positive controls after a 14-day photothermal therapy with less < 5% necrosis resulting from non-specific ablation (negative control). Further magnetic-based imaging of fixed-tumor sample showed T2 contrast enhancement (> 50%) resulting from the accumulation of these HNPs. The use of HNPs for in vivo therapy and diagnosis (theranostics) applications is demonstrated.
Section snippets
Materials
All chemicals were of reagent grade and used without further purification. N-hydroxylsulfosuccinimide (Sulfo-NHS), and 1-ethyl-3-(3-dimethylaminopropyl carbodiimide HCl (EDC) were purchased from Pierce Biotechnology(Rockford, IL); Alexa Fluor® 750 succinimidyl ester was purchased from Invitrogen; Avertin solution was purchased from Sigma-Aldrich (St. Louis, MO); Matrigel was purchased from BD Biosciences (Bedford, MA); SW1222 cells (antigen-expressing colorectal cancer cell line) and
Nanoparticle conjugation and characterization
We have previously reported the synthesis and functionalization of 6–18 nm HNPs that resulted in stabile, biocompatible nanoparticles (supporting information). The HNPs showed enhanced optical absorbance in the near-IR region as compared to homofunctional iron oxide nanoparticles of comparable size.22 This suggests that HNPs can also be used for photothermal therapy (supporting information). To prepare particles for targeted delivery, HNPs were conjugated to A33scFv through carboxyl groups and
Discussion
In this work, we demonstrated the use of HNPs as multifunctional theranostic platform for in vivo applications. The HNPs were selectively targeted to antigen-expressing cells using a single-chain antibody (A33scFv). In this conformation, iron oxide NP portion of HNPs serves as MR imaging agent while the gold NP portion functions as an hyperthermia agent. As a MR imaging agent, HNPs were tested in xenografted subcutaneous colorectal cancer tumors where post-contrast phase T2* value was reduced
Acknowledgments
The authors gratefully acknowledge Xiaoyue Chen, Department of Biomedical Engineering for assistance and training on animal handling. They also acknowledge Dr. Tian Li, Department of Radiology at Weill Medical College of Cornell University for MR imaging and Richard Wong for help with MR data analyses.
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Disclosure of conflict of interest: The authors acknowledge that no conflicts of financial or commercial interests exist with this manuscript.
Acknowledgments of funding supports: The authors acknowledge Graduate fellowship from Sloan Foundation and the Ludwig Institute for Cancer Research for support.