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Magn Reson Med. 2013 Dec;70(6):1748-60. doi: 10.1002/mrm.24622. Epub 2013 Feb 7.

Induced clustered nanoconfinement of superparamagnetic iron oxide in biodegradable nanoparticles enhances transverse relaxivity for targeted theranostics.

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Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.



Combined therapeutic and diagnostic agents, "theranostics" are emerging valuable tools for noninvasive imaging and drug delivery. Here, we report on a solid biodegradable multifunctional nanoparticle that combines both features.


Poly(lactide-co-glycolide) nanoparticles were engineered to confine superparamagnetic iron oxide contrast for magnetic resonance imaging while enabling controlled drug delivery and targeting to specific cells. To achieve this dual modality, fatty acids were used as anchors for surface ligands and for encapsulated iron oxide in the polymer matrix.


We demonstrate that fatty acid modified iron oxide prolonged retention of the contrast agent in the polymer matrix during degradative release of drug. Antibody-fatty acid surface modification facilitated cellular targeting and subsequent internalization in cells while inducing clustering of encapsulated fatty-acid modified superparamagnetic iron oxide during particle formulation. This induced clustered confinement led to an aggregation within the nanoparticle and, hence, higher transverse relaxivity, r2 , (294 mM(-1) s(-1) ) compared with nanoparticles without fatty-acid ligands (160 mM(-1) s(-1) ) and higher than commercially available superparamagnetic iron oxide nanoparticles (89 mM(-1) s(-1) ).


Clustering of superparamagnetic iron oxide in poly(lactide-co-glycolide) did not affect the controlled release of encapsulated drugs such as methotrexate or clodronate and their subsequent pharmacological activity, thus highlighting the full theranostic capability of our system.


PLGA; clodronate; clustered; iron oxide; methotrexate; targeted

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