Original Article
Targeted near-IR hybrid magnetic nanoparticles for in vivo cancer therapy and imaging

https://doi.org/10.1016/j.nano.2012.11.009Get rights and content

Abstract

We report the use of immuno-targeted gold–iron oxide hybrid nanoparticles for laser-assisted therapy and for MRI-based imaging as demonstrated in xenograft colorectal cancer tumor model. Immuno-targeted gold–iron oxide nanoparticles selectively accumulate in SW1222 xenograft tumors as compared to the accumulation in non-antigen-expressing tumor xenografts. Effective photothermal treatment using near-IR laser irradiation (808 nm, 5 W cm 2) application is shown where > 65% of the antigen-expressing tumor cells presented corrupt extracellular matrix and cytoplasmic acidophilia suggesting effectiveness of nanoparticle-assisted thermal therapy. Cell killing was confirmed by hematoxylin and eosin (H&E) histological staining where scar-like structure containing collagen bundles was observed in the treatment group. Further, systemically injected HNPs were shown to be effective T2 magnetic resonance (MR) imaging contrast agents, localized and detected at the antigen-expressing xenograft tumors. These findings suggest that the new class of bio-conjugated HNPs exhibits great potential for dual-therapy and diagnostics (theranostics) applications.

From the Clinical Editor

This team reports the successful use of immuno-targeted gold-iron oxide hybrid nanoparticles for both laser-assisted therapy and MRI-based imaging in a xenograft colorectal cancer tumor model, demonstrating strong potentials for dual applications in cancer diagnosis and therapy.

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.

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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.

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