- The drug is wrapped in a microcapsule that can navigate towards cancer cells
- Millions of these tiny capsules could be injected into the bloodstream
- The outer layer of the capsule would prevent damage to healthy tissue
- Using an ultrasound machine, doctors could trigger the microcapsules to rupture when they reach a solid tumor, releasing the cancer killing drug
Researchers have designed tiny cancer-fighting microcapsules that can navigate themselves towards cancerous tumors in the body.
The multilayer capsule contains an anti-cancer drug which can be released via an ultrasound trigger, working as a guided drug delivery system.
The new technology could offer a noninvasive alternative to cancer surgeries or chemotherapy.
The microcapsules allow researchers to detect them with ultrasound, and also rupture them with therapeutic higher-dose ultrasound. Pictured is a schematic of the multilayer capsule, with the image on the right showing a ruptured capsule triggered by ultrasound. Left is a scan of the capsules, which can be easily detected by ultrasound
The capsule, designed by researchers at the University of Alabama at Birmingham (UAB), has three traits that have been difficult to achieve all together in a single cancer drug.
They’re easily detectable via low-power ultrasound, they can safely and efficiently encapsulate the cancer drug doxorubicin, and a dose of ultrasound can trigger the release of the drug.
Doxorubicin is a chemotherapy drug that’s used to treat several types of cancer.
The capsule can target cancerous tumors and the controlled release mechanism spares the rest of the body from dose-limiting toxicity.
HOW DOES IT WORK?
The microcapsules contain the cancer fighting drug doxorubicin, wrapped within a protective coating.
These microcapsules prevent damage to healthy tissue and allow medications to slip past the body’s drug-clearance systems.
Infographic explaining how the microcapsules work in the body to target cancer cells while avoiding damage to healthy tissue
It function in 4 steps:
- Tiny, hollow microcapsules, each smaller than a red blood cell, are created layer by layer in a lab.
- Each microcapsule contains the cancer drug doxorubicin.
- Millions of these microcapsules could be injected into the bloodstream. The durable outer layer would keep the cancer drug away from healthy tissue as the microcapsules travel to the tumor site.
- Using an ultrasound machine, doctors could trigger the microcapsules to rupture when they reach a solid tumor, releasing the cancer-killing drug.
‘We envision an entirely different approach to treating solid human tumors of numerous pathologic subtypes, including common metastatic malignancies such as breast, melanoma, colon, prostate and lung, utilizing these capsules as a delivery platform,’ said Dr Eugenia Kharlampieva, an associate professor in the Department of Chemistry at UAB and the lead author of the study.
‘These capsules can protect encapsulated therapeutics from degradation or clearance prior to reaching the target and have ultrasound contrast as a means of visualizing the drug release.
‘They can release their encapsulated drug cargo in specific locations via externally applied ultrasound exposure.’
Dr Karlampieva said there is an urgent, so far unmet need for such an easily fabricated drug delivery system.
The researchers built the microcapsules using alternating layers of biocompatible tannic acid and poly(N-vinylpyrrolidone), or TA/PVPON.
Tannic acid has widespread uses including as an aroma compound in soft drinks and juices, and as a medication in antidiarrheal agents and even as an antiallargen in allergy sprays.
TA/PVPON is a large molecule that has many applications including the production of mebranes for dialysis, as an aid to increase the solubility of drugs and even as an adhesive in glue stick.
The layers of the capsule are formed around a core of solid silica or porous calcium carbonate that is dissolved after the layers are complete.
Varying the number of these layers, as well as the weight of the material or the ratio of shell thickness to capsule diameter, can alter their sensitivity to ultrasound for detection in the body to levels below the FDA maximum for clinical imaging and diagnosis.
Experiments conducted by the researchers showed that the ratio of the thickness of the capsule wall to the diameter of the capsule is a key variable for sensitivity to rupture and release the drug.
To test the ultrasound imaging properties of the microcapsules, the researchers made capsules that were 5 micrometers wide – smaller than a red blood cell.
Capsules of this size that were made with eight layers showed an ultrasound contrast comparable to a commercially available ultrasound contrast agent called Definity – so they were easily visible in the body.
(a) Schematic illustration of the multilayer capsules loaded with doxorubicin – with the inset (top left) showing a cross-section of the capsule. (b) Schematic representation of a ruptured capsule, triggered by ultrasound. Following its destruction, doxorubicin is released
But the capsules that the researchers developed for the drug delivery mechanism are much smaller than this – with a shell thickness of 50 nanometers.
When these were loaded with the anti-cancer drug, the ultrasound imaging contrast increased two-to eightfold compared to empty capsules – making them easier to see.
The drug-containing capsules were highly stable and showed no change in ultrasound imaging detection after being stored away for six months.
When testing how the particles rupture, the researchers found that a therapeutic dose of ultrasound was able to rupture 50 per cent of the the larger 5-micrometer capsules, releasing enough doxorubicin to induce 97 percent cell toxicity in human breast cancel cells in culture.
(c,d, e) Images of different sized multilayer capsules. When testing how the particles rupture, the researchers found that a therapeutic dose of ultrasound was able to rupture 50 per cent of the the larger 5-micrometer capsules, releasing enough doxorubicin to induce 97 percent cell toxicity in human breast cancel cells in culture
Cancer cells that were incubated with the capsule without receiving a dose of ultrasound had no effect on the cancer cells, so the ultrasound trigger is crucial to the drug delivery method.
Dr Kharlampieva said that the capsules have strong potential as ‘theranostic’ agents for efficient cancer therapy in conjunction with ultrasound.
Theranostic refers to nanoparticles or microcapsules that can double as diagnostic imaging agents and as therapeutic drug-delivery carriers.
The next important preclinical step, Dr Kharlampieva says, will be to study the capsules in animals to explore how long the capsules persist in blood circulation and where they distribute in the body.
The research team, left to right: Dr Eugenia Kharlampieva, Dr Jun Chen, Sithira Ratnayaka, Dr Veronika Kozlovskaya and Aaron Alford