Abstract
Microbubbles and nanobubbles (MNBs) can be prepared using various shells, such as phospholipids, polymers, proteins, and surfactants. MNBs contain gas cores due to which they are echogenic and can be used as contrast agents for ultrasonic and photoacoustic imaging. These bubbles can be engineered in various sizes as vehicles for gas and drug delivery applications with novel properties and flexible structures. Hypoxic areas in tumors develop owing to an imbalance of oxygen supply and demand. In tumors, hypoxic regions have shown more resistance to chemotherapy, radiotherapy, and photodynamic therapies. The efficacy of photodynamic therapy depends on the effective accumulation of photosensitizer drug in tumors and the availability of oxygen in the tumor to generate reactive oxygen species. MNBs have been shown to reverse hypoxic conditions, degradation of hypoxia inducible factor 1α protein, and increase tissue oxygen levels. This review summarizes the synthesis methods and shell compositions of micro/nanobubbles and methods deployed for oxygen delivery. Methods of functionalization of MNBs, their ability to deliver oxygen and drugs, incorporation of photosensitizers and potential application of photo-triggered theranostics, have also been discussed.
Highlights
The lack of oxygen, known as hypoxia, is a common characteristic of solid tumors, which results in reduced therapeutic response and malignant progression [1,2,3]
This review provides a general overview of Microbubbles and nanobubbles (MNBs) used as a source of oxygen to reverse hypoxia and hypoxemia during the last two decades
To test the applications of MNBs for oxygen delivery, researchers have tested the mechanisms by oxygen delivery to deoxygenated water, cells under hypoxic conditions, and animals kept in hypoxemia models
Summary
The lack of oxygen, known as hypoxia, is a common characteristic of solid tumors, which results in reduced therapeutic response and malignant progression [1,2,3]. Nanobubbles have been investigated for diagnostic and therapeutic purposes owing to their nanometer size, for enhancing cellular penetration of these bubbles [22,26,27,28,29,30,31]. Various other researchers have 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 a 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].
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