Gadolinium/DOTA functionalized poly(ethylene glycol)-block-poly(acrylamide-co-acrylonitrile) micelles with synergistically enhanced cellular uptake for cancer theranostics

The combination of diagnostic and therapeutic functions into a nano-carrier could achieve a delivery system with both accurate diagnosis and delivery capabilities. Herein, a functionalized polymer of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-poly(ethyleneglycol)-block-poly(acrylamide-co-acrylonitrile) (DOTA-PEG-b-poly(AAm-co-AN)) was designed and synthesized. Doxorubicin (DOX) and gadolinium ions (Gd3+) were loaded into the hydrophobic core and chelated on the shell of the micelles during the self-assembling process to endow the prepared micelles with drug delivery and magnetic resonance imaging functionalities. Such theranostics micelles exhibited noticeable accelerated DOX release with elevated temperature and high proton relaxivity r1 (25.88 mM−1 s−1). Moreover, the Gd3+/DOX loaded micelle presented a synergistically enhanced cellular uptake efficiency (2.12 times that of free DOX) as compared with free drug or that loaded in micelles without Gd3+. The micelles provide promising application for chemotherapy and simultaneous enhanced magnetic resonance imaging (MRI) of cancer.

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