Engineering oxygen nanobubbles for the effective reversal of hypoxia

Abstract

Hypoxia, which results from an inadequate supply of oxygen, is a major cause of concern in cancer therapy as it is associated with a reduction in the effectiveness of chemotherapy and radiotherapy in cancer treatment. Overexpression and stabilization of hypoxia-inducible factor 1α (HIF-1α) protein in tumours, due to hypoxia, results in poor prognosis and increased patient mortality. To increase oxygen tension in hypoxic areas, micro- and nanobubbles have been investigated by various researchers. In the present research, lipid-shelled oxygen nanobubbles (ONBs) were synthesized through a sonication method to reverse hypoxic conditions created in a custom-made hypoxic chamber. Release of oxygen gas from ONBs in deoxygenated water was evaluated by measuring dissolved oxygen. Hypoxic conditions were evaluated by performing in vitro experiments on MDA-MB231 breast cancer cells through the expression of HIF-1α and the fluorescence of image-iT™ hypoxia reagent. The results indicated the degradation of HIF-1α after the introduction of ONBs. We propose that ONBs are successful in reversing hypoxia, downregulating HIF-1α, and improving cellular conditions, leading to further medical applications.

Parameters Influencing Size of Micro Nano Bubble

“…The oxygen concentration was increased in hypoxic areas by using oxygen micro-nanobubbles which were prepared by using different methods. The results indicated the degradation of HIF-1α after the introduction of ONBs [2]. They were also reported to be used in different imaging methods for medical applications.…”

“…This many applications of such tiny and generally ignored object make it worthy to be explored more. Nanobubble has been used for detergent-free cleaning, ultra-sound imaging and intracellular drug delivery like one research has showed their application in drug release in intracellular hyperthermia [9], enhanced drug susceptibility of cancer cells [2], and mineral processing for dispersing Kaolinite and talc in aqueous solution [10] etc.For the last few decades this technology has seen a steep rise. This technology holds really good potential and more and more experimentation and research should be done.…”

Applications of Oxygen-Carrying Micro/Nanobubbles: a Potential Approach to Enhance Photodynamic Therapy and Photoacoustic Imaging

“…Various combinations of base phospholipids, such as 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) have been used by researchers in combination with various surfactants and emulsifiers, including PEGylated lipids [20,61]. Polyethylene glycol (PEG) is highly hydrophilic with low toxicity, and it is used to improve stability and surface modification and avoid coalescence [11,62,63].…”

“…Electrochemical sensing has also been applied to measure the dissolved oxygen content in a solvent subsequent to the injection of oxygen containing MNBs in a deoxygenated solvent [13]. Fluorescence quenching uses a live cell imaging technique when cells are under hypoxia, and it can be used to evaluate the performance of MNBs to reverse hypoxia [20,76]. Fiber-optic based sensors have also been employed to measure a change in oxygen concentration owing to the MNBs [5].…”

“…Various other researchers have also investigated nanobubbles as ultrasound contrast agents for tumor imaging and drug/gene delivery applications [2,31,[33][34][35]. Compared to nanosized liposomes, which contain lipid bilayer membrane and hydrophilic aqueous core, nanobubbles have monolayer shells encapsulating a hydrophobic gas core, making them feasible for gas delivery applications [20,26,36,37]. Both microsized and nanosized bubbles have been used for oxygen delivery [15].…”