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

Abstract

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.