Anti-cancer bubbles
Microbubbles will improve alternative therapy against cancer
Skoltech blog, Naked Science
The study was published in the journal Colloids and Surfaces B: Biointerfaces (Barmin et al., Albumin microbubbles conjugated with zinc and aluminum phthalocyanine dies for enhanced photodynamic activity). "Photodynamic therapy is arranged as follows: a photosensitizing drug is injected into the patient's blood, after which the tumor is irradiated with light either directly through the skin or using an endoscope. The wavelength of light is selected for the drug so that it absorbs light and initiates the generation of singlet oxygen and free radicals, the local action of which affects cells in the area affected by light," explained Dmitry Gorin, head of the study, professor at the Center for Photonics and Photonic Technologies of Skoltech.
The first author of the article, a graduate of the Skoltech Master's degree, Roman Barmin, commented on the work as follows: "We have shown on two popular photosensitizing drugs that their photoactivity increases when binding to the protein albumin from bovine serum, and if the resulting protein —drug conjugate is whipped up until bubbles appear, then the effectiveness increases even more. All this is applicable in photodynamic therapy of malignant tumors."
In their experiments, the research team used two photosensitizers: for zinc and aluminum phthalocyanines, covalent and electrostatic bonding with albumin was shown, respectively. The first drug has already been approved for use in photodynamic therapy, the second is undergoing clinical trials. As for the production of bubbles, the albumin-phthalocyanine solution is "whipped" with ultrasound, selecting the appropriate frequency and temperature for this.
"Microbubble drug delivery is an actively developing technology, but we considered albumin bubbles in relation to photodynamic therapy for the first time, and these two photosensitizers — in the context of bubbles — too," said Barmin. "The convenience of bubbles is that photosensitizer molecules can be packed very tightly into their shell, and it is possible to collapse the bubbles and release the encapsulated drug by ultrasound."
Laboratory tests have shown that the delivery of the drug by bubbles into cells works well. "Now our goal is to get a more complete understanding of the interaction of microbubbles with cells in order to find ways to increase the therapeutic effect," Gorin added. After investigating the properties of microbubbles, the team came to the conclusion that the conjugation of microbubbles with a photosensitizer changes the physicochemical properties. The size of the bubbles on average does not differ from bubbles without phthalocyanins (such are used for ultrasound as a contrast agent), which is useful for monitoring their action, and at the same time increases the concentration of bubbles and their stability during storage.
"The next step was to understand whether the photosensitizer efficiency would be higher with microbubbles than without them," Barmin said. — Our colleagues from the IOF RAS have developed a method by which this can be tested on red blood cell suspensions. He clearly showed that in the case of both drugs, the conjugate of phthalocyanin and albumin was more effective than phthalocyanins themselves, and with microbubble delivery, the effectiveness increased even more. The reason is precisely in the dense packaging of the drug molecules in the bubble shell." Photodynamic antitumor therapy is an example of the entry of two technologies traditionally used in diagnostics, ultrasound and microbubbles, into the field of therapy.
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