Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles

Abstract

Oxygen homeostasis is important in the regulation of biological function. Disease progression can be monitored by measuring oxygen levels, thus producing information for the design of therapeutic treatments. Non-invasive measurements of tissue oxygenation require the development of tools with minimal adverse effects and facile detection of features of interest. Fluorine magnetic resonance imaging (19F-MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for anatomical imaging, cell tracking, and oxygen sensing. However, the highly hydrophobic and lipophobic properties of perfluorocarbons require the formation of emulsions for biological studies. Though, stabilizing these emulsions has been challenging. To enhance the stability and biological loading of perfluorocarbons, one option is to incorporate perfluorocarbon liquids into the internal space of biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19F-MRI detectable oxygen sensing probes. Ultraporous mesostructured nanoparticles (UMNs) have large internal cavities (average = 1.76 cm3 g−1), facilitating an average 17% loading efficiency of PFCs, meeting the threshold fluorine concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs have the highest equivalent nuclei per PFC molecule, and a spin-lattice (T1) relaxation-based oxygen sensitivity of 0.0032 mmHg−1 s−1 at 16.4 T (657 MHz). The option of loading PFCs after synthesizing UMNs, rather than the more traditional in situ core-shell syntheses, allows for use of a broad range of PFC liquids from a single material. The biocompatible and tunable chemistry of UMNs combined with the intrinsic properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical imaging, cell tracking, and metabolic spectroscopy with improved stability.

Partially Fluorinated Copolymers as Oxygen Sensitive 19F MRI Agents

“…The 19 FMRI signal enhancement correlated directly with an increase in sensitivity for detecting pO 2 ,w ith the best materials demonstrating an oxygen sensitivity of 240 (10 À5 mmHg À1 s À1 ). Notably,t his sensitivity is similar to emulsified PFC-based materials, [23,27] and is the first report of watersoluble 19 FMRI agents demonstrating the capacity for non-invasive quantification of pO 2 .…”

“…These results compare favorably with recently reportedP FC-loaded silica nanoparticles, whicha chieveda no xygen sensitivity of 334 10 À5 mmHg À1sÀ1 . [27] These results imply that water-soluble 19 FMRI agentsa re competitive materials compared to encapsulatedf luorocarbonsf or oxygen sensing, and that increasing the incorporation of fluorinated comonomer improves pO 2 sensitivity.W ith these structure-property relationshipse stablished, future work will focus on exploring the utility of these materials within the physiologically relevant pO 2 range, which include hypoxic tumors ( % 7mmHg O 2 ), peripheralt issues ( % 40 mmHg O 2 ), and venous and arterial blood ( % 50 and % 70 mmHg O 2 ,respectively). [75]…”

“…[14][15][16][17][18][19][20] Due to the instability of PFCe mulsions, [21,22] encapsulating PFCs into alginatec apsuleso rs ilica nanoparticles has recently been pursued. [23][24][25][26][27] Lastly,h ypoxia-responsive 19 F probesu tilizing paramagnetic relaxation enhancement (PRE) have been shown to accumulate selectively in hypoxic cells, [28][29][30][31] but the low loading of 19 Fn uclei limits their sensitivity.…”

Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking

“…All imaging agents described thus far that contain a liquid PFC have a core‐shell‐like structure, where the liquid PFC droplet is coated with a lipid or polymer shell. A significant improvement of stability can be achieved by the encapsulation of PFCs in inorganic shells, such as silica . However, while well‐suited for in vivo applications, these materials still have to pass approval for clinical use.…”

A Multifunctional Biomimetic Nanoplatform for Relieving Hypoxia to Enhance Chemotherapy and Inhibit the PD‐1/PD‐L1 Axis

“…On the other hand, to relieve the hypoxia, researchers have carried out lots of investigations, such as photocatalyzed water splitting by carbon nitride, dissolved O 2 delivering by perfluorocarbon, in situ H 2 O 2 decomposing by catalase (CAT) or MnO 2 . However, it is necessary to address tumor‐specific O 2 release to assure therapeutic efficiency and avoid potential systemic side effects, which has been reported in clinically approved hyperbaric oxygen therapy .…”