Lipid nanocapsules as in vivo oxygen sensors using magnetic resonance imaging.

Hypoxia is common occurrence of the tumour microenvironment, wherein heterogeneous gradients of O2 give rise to tumoural cells which are highly malignant, metastatic, and resistant to therapeutic efforts. Thus, the assessment and imaging of hypoxia is essential for tumour diagnosis and treatment. Magnetic resonance imaging and, more specifically, the quantitative assessment of longitudinal relaxation time enhancement, was shown to enable the mapping of oxygen in tumours with increased sensitivity for lipids as compared to water signal. Unfortunately, this can only be applied to tumours with high lipid content. To overcome this issue, we propose the use of lipid nanocapsules (LNCs). LNCs have been demonstrated as excellent core-shell nanocarriers, wherein the lipidic-core is used for lipophilic drug encapsulation, enabling treatment of highly malignant tumours. Herein, however, we exploited the lipidic-core of the LNCs to develop a simple but effective technique to increase the lipidic content within tissues to enable the assessment and mapping of pO2. LNCs were prepared using the phase-inversion technique to produce 60 nm sized nanoparticles, and in vitro studies demonstrated the permeability and responsiveness of LNCs to O2. To evaluate the ability of LNCs to respond to changes in pO2in vivo, after a hyperoxic challenge, three animal models, namely a normal tissue model (gastrocnemius muscle tissue) and two tumour tissue models (subcutaneous fibrosarcoma and intracerebral glioblastoma) were explored. LNCs were found to be responsive to variation of O2in vivo. Moreover, the use of MRI enabled the mapping of oxygen gradients and heterogeneity within tumours.