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.

Hypoxia is a key concern during the treatment of tumors, and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor resistance to therapeutic modalities. In this study, doxorubicin-loaded oxygen nanobubbles (Dox/ONBs) were synthesized, and the effectiveness of drug delivery to MDA-MB-231 breast cancer and HeLa cells was evaluated. Dox/ONBs were characterized using optical and fluorescence microscopy, and size measurements were performed through nanoparticle tracking analysis (NTA). The working mechanism of Dox was evaluated using reactive oxygen species (ROS) assays, and cellular penetration was assessed with confocal microscopy. Hypoxic conditions were established to assess the effect of Dox/ONBs under hypoxic conditions compared with normoxic conditions. Our results indicate that Dox/ONBs are effective for drug delivery, enhancing oxygen levels, and ROS generation in tumor-derived cell lines.

Liquid metals are being studied intensively because of their potential as a drug delivery system. Eutectic gallium–indium (EGaIn) alloy liquid metals have a low melting point, low toxicity, and excellent tissue permeability. These properties may enable them to be vascular embolic agents that can be deformed by light or heat. In this study, we developed EGaIn particles that can deliver anticancer drugs to tumor cells in vitro and change their shapes in response to external stimuli. These particles were prepared by sonicating a solution containing EGaIn and amphiphilic lipids. The liquid metal (LM)/amphiphilic lipid (DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholin) particles formed a vehicle for doxorubicin, an anticancer drug, which was released (up to 50%) when the shape of the particles was deformed by light or heat treatment. LM/DSPC particles are non-toxic and LM/DSPC/doxorubicin particles have anticancer effects (resulting in a cell viability of less than 50%). LM/DSPC/doxorubicin particles were also able to mimic blood vessel embolisms by modifying their shape using precisely controlled light and heat in engineered microchannels. The purpose of this study was to examine the potential of EGaIn materials to treat tumor tissues that cannot be removed by surgery.

Phospholipids have been widely investigated for the preparation of liposomes, and micro and nanobubbles. They comprise biocompatible and biodegradable molecules and offer simple preparation with a variety of functions in diagnostic and therapeutic applications. Phospholipids require emulsifiers and surfactants to assemble in the form of bubbles. These surfactants determine the size, zeta potential, and other characteristics of particles. Polyethylene glycol (PEG) and its various derivatives have been employed by researchers to synthesize micro and nanobubbles. The stability of phospholipid-shelled nanobubbles has been reported by various researchers owing to the reduction of surface tension by surfactants in the shell. Nanobubbles have been employed to deliver oxygen to tissues and hypoxic cells. In this study, we investigated the effects of different ratios of phospholipids to PEG on the size, distribution, and characterization of oxygen nanobubbles (ONBs). ONBs were synthesized using a sonication technique. We analyzed and compared the sizes, numbers of generated particles, and zeta potentials of different compositions of ONBs using dynamic light scattering and nanoparticle tracking analysis. Then, we employed these oxygen nanobubbles to enhance the cellular microenvironment and cell viability. ONBs were also investigated for ultrasound imaging.

Developing synthetic biological devices to allow the noninvasive control of cell fate and function, in vivo can potentially revolutionize the field of regenerative medicine. To address this unmet need, we designed an artificial biological “switch” that consists of two parts: (1) the electromagnetic perceptive gene (EPG) and (2) magnetic particles. Our group has recently cloned the EPG from the Kryptopterus bicirrhis (glass catfish). The EPG gene encodes a putative membrane-associated protein that responds to electromagnetic fields (EMFs). This gene’s primary mechanism of action is to raise the intracellular calcium levels or change in flux through EMF stimulation. Here, we developed a system for the remote regulation of [Ca²⁺]_i (i.e., intracellular calcium ion concentration) using streptavidin-coated ferromagnetic particles (FMPs) under a magnetic field. The results demonstrated that the EPG-FMPs can be used as a molecular calcium switch to express target proteins. This technology has the potential for controlled gene expression, drug delivery, and drug developments.

We aimed to design and manufacture a transporter capable of delivering small interfering RNAs (siRNAs) into the skin without causing any damage. β-glucans are unique chiral polysaccharides with well-defined immunological properties and supramolecular wrapping ability. However, the chiral properties of these polymers have hardly been applied in drug delivery systems. In this study, β-glucan nanoparticles were designed and manufactured to deliver genetic material to the target cells. The β-glucan molecules were self-assembled with an siRNA into nanoparticles of 300–400 nm in diameter via a conformational transition process, in order to construct a gene delivery system. The assembled gene nanocarriers were associated with high gene-loading ability. The expression and efficiency of siRNA were verified after its delivery via β-glucan. Our results provide evidence that β-glucan nanoparticles can be effectively used to deliver siRNA into the cells.