Nonclustered magnetite nanoparticle encapsulated biodegradable polymeric micelles with enhanced properties for in vivo tumor imaging

Copolymers of poly(ethylene glycol) and poly(ε-caprolactone) bearing folate as a targeting molecule, i.e. Fa-PEG-PCL, are synthesized and employed to encapsulate nonclustered superparamagnetic iron oxide nanoparticle (SPION) to achieve a water-dispersible and tumor-targeted MRI contrast agent. Compared to the water-soluble SPIONs prepared by small molecular surfactant coating, the nonclustered SPIO-encapsulated PEG-PCL micelles (PEG-PCL-SPIONs) simultaneously display increased transversal (r₂) and much decreased longitudinal (r₁) magnetic resonance relaxivities, leading to high r ₂/r₁ ratios which make PEG-PCL-SPIONs highly sensitive MRI T₂ contrast agents. Animal experiments are carried out by injecting the micelle solutions via a tail vein into nude mice bearing subcutaneous xenografts of human Bel 7402 hepatoma. Notably, the nonclustered SPIO-encapsulated micelles measuring 35 nm on average based on PEG4.3k-PCL1k display much slower liver accumulation implying prolonged circulation, compared to the clustered SPIO-encapsulated micelles (125 nm) based on PEG4.3k-PCL7.2k. Furthermore, injection of the small-sized and folate-targeted micelle, i.e. Fa-PEG4.3k-PCL1k-SPION, result in obviously shortened MRI T₂ as well as much decreased MRI signal intensity within the tumor section, implying efficient accumulation of the micelles which is also demonstrated by prussian blue staining of the tumor tissue. Our results reveal the great potential of the nonclustered SPIO-encapsulated and small-sized micelle with active tumor-targeting function as an effective MRI probe for in vivo tumor detection.