We describe the development of multifunctional polymeric micelles with cancer-targeting capability via alpha(v)beta(3) integrins, controlled drug delivery, and efficient magnetic resonance imaging (MRI) contrast characteristics. Doxorubicin and a cluster of superparamagnetic iron oxide (SPIO) nanoparticles were loaded successfully inside the micelle core. The presence of cRGD on the micelle surface resulted in the cancer-targeted delivery to alpha(v)beta(3)-expressing tumor cells. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI imaging and alpha(v)beta(3)-specific cytotoxic response of these multifunctional polymeric micelles.

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Polymer micelles are rapidly becoming a powerful nanomedicine platform for cancer therapeutic applications due to their small size (10-100 nm), in vivo stability, ability to solubilize water insoluble anticancer drugs, and prolonged blood circulation times. Recent data from clinical trials with three micelle formulations have highlighted these and other pharmacokinetic advantages with reduced systemic toxicity and patient morbidity compared to conventional drug formulation. While the initial anti-tumor efficacy of these systems seems promising, a strong research impetus has been placed on micelle functionalization in order to achieve tumor targeting and site-specific drug release, with the hope of reaching a more pronounced tumor response. Hence, the purpose of this review is to draw attention to the new developments of multi-functional polymer micelles for cancer therapy with special focus on tumor targeting and controlled drug release strategies.

Targeting micelles: Cyclic pentapeptide cRGDfK (red triangles), which targets integrin αvβ3, was conjugated to the outer shell of doxorubicin‐loaded (red hexagons) polymeric micelles by using a post‐micelle modification method. The modified micelles significantly enhanced their internalization (up to 30‐fold) by receptor‐mediated endocytosis in tumor endothelial cells overexpressing the αvβ3 receptor.