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Table 4 Fuels types of MOF-NZs micro-/nano-motors

From: Explaining chemical clues of metal organic framework-nanozyme nano-/micro-motors in targeted treatment of cancers: benchmarks and challenges

H2O2

Properties

H2O2 is available in all aerobic metabolism, and it is generated via an extracellular and intracellular proceeding. The mitochondrial electron transport chain, the arachidonic acid metabolizing lipoxygenase and cyclooxygenase, the cytochrome P450s, xanthine oxidase, NAD(P)H oxidases, uncoupled nitric oxide synthase and peroxidases can be potential sources of H2O2 enzymatic. Tumor cells generated more H2O2 than normal cells

Limitation

H2O2 is harmful to cells when it reaches a certain concentration of 50 µM < , resulting in the oxidation of DNA, lipids and proteins

Mechanism

H2O2 is decomposed into water and oxygen bubbles, that oxygen bubbles provide the force to motors as a bubble propulsion

Water

Properties

Water is a liquid available in various tissues and biocompatible that can be highly regarded as a local fuel for nano-/micro-motors. The hydrogen bubbles resulting from the reaction between the active metal NPs such as Mg, Pt, Al, Ti, Ga, and water are responsible for propelling

Limitation

Accumulation of H2 in the tissue increases the possibility of acidification in the presence of CO2. On the other hand, despite the positive value of H2 accumulation in tissues to reduce free radicals and reduce apoptosis, in cancer tissues this feature will be considered as a negative factor

Mechanism

Based on the chemical reaction between nano metals and water

Urea

Properties

Urea, which is generally produced by amino acid catabolism, is a source of excreted nitrogen to reduce nitrogen toxicity in the body. Urea is produced in the liver and transported from the blood to the kidneys for excretion. Also, some is excreted by the gastrointestinal tract. Diseases such as hepatitis, cirrhosis of the liver and kidney problems cause an increase in urea in the blood

Limitation

The minimum concentration of urea expected to move the motor is 50 mM, which is difficult and sometimes impossible to achieve in biological fluids, except in urine. High concentrations of urea increase the risk of meth-hemoglobin poisoning

Mechanism

Urea is hydrolyzed to ammonium ions and bicarbonate anions by urease. By increasing the urease function, the formation of a local electric field due to the accumulation of ammonium ions is enhanced, which leads to the movement of the motor

Glucose

Properties

Blood glucose based on nutrients consumed and glucose production in the liver (through metabolic pathways such as glycogenesis, glycogenolysis and gluconeogenesis) is regulated. In solid tumors, glucose levels are lower than normal tissues due to a disordered vascular system, dysfunctional capillary substrate, and faster metabolism. Therefore, the tendency of glucose to enter tumors will be very high

Limitation

Motors move (in response to the glucose gradient) toward areas with higher glucose concentrations. Therefore, the possibility of motor transmission to some cells or target tissues is difficult due to low glucose concentration. In addition, there is a possibility of hypoglycemia in the target tissue by the motors

Mechanism

Glucose by GOx can be converted into glucuronic acid and H2O2. The generated H2O2 can subsequently be decomposed into harmless oxygen and water by CAT to power motors. In order to achieve a stable motion at a constant speed, the integration of GOx and CAT are considered

ATP

Properties

ATP is generated from ADP and mineral phosphate by F1F0-ATP synthase. ATP plays a key role in many processes such as muscle contraction, synthesis and degradation of biological molecules, and cellular signaling. Plasma ATP concentration in humans is determined at 1 mmol/L, while the intracellular concentration varies between 1–10 mmol/L based on cell function

Limitation

An imbalance in the use of ATP increases the possibility of ADP accumulation, which inhibits adjacent bio-motors or motors. Also, adenosine accumulation due to off-targeted degradation of ATP outside the cell becomes highly toxic to cells

Mechanism

ATP decomposition to release chemical energy

Acid

Properties

Biological acids such as stomach acid or acidic environments created in cancerous tissues or repairing tissues are a source of energy for nano-/micro-motors. The limitation of acidic environments in the body can provide the amount of nano-/micro-motors movement in a limited environment in addition to the possibility of targeting the nano-/micro-motors

Limitation

An unusual corrosion of motors in an acidic environment can reduce their performance, and activated metal NPs activate unpredictable pathways. On the other hand, the reduction of the environment acidity caused by rapid evacuation of protons by motors has negative effects on the activity of some organs such as the stomach

Mechanism

A reaction between the nano- or micro-motor and the surrounding protons, generates H2 bubbles