A new system for delivering targeted cancer therapies has been developed by researchers in China and Sweden. The biodegradable drug-delivery system uses an external light source to degrade black phosphorous (BP) hydrogel nanostructures containing drugs for cancer therapies. As the structure degrades, it releasesA new system for delivering targeted cancer therapies has been developed by researchers in China and Sweden. The biodegradable drug-delivery system uses an external light source to degrade black phosphorous (BP) hydrogel nanostructures containing drugs for cancer therapies. As the structure degrades, it releases the drugs at tumour sites. the drugs at tumour sites.
Targeted drug delivery to tumours is a very attractive option for cancer therapies as it provides treatment directly at the point of the tumour. However, localized approaches such as injections of chemotherapy drugs are invasive, and are often painful. Polymer-based drug-delivery systems that are inserted into the body and degrade to release drugs are encouraging, but often cannot be controlled. The result is therapies that don’t work, which contributes to the increased risk of resistance in cancer cells.
The team led by Han Zhang at the Shenzhen University, China, and Yihai Cao at the Karolinska Institutet, Sweden trialled the use of black phosphorous. The newly discovered material boasts high photothermal conversion efficiency, easy fabrication and excellent biocompatibility and biodegradation. Their BP@Hydrogel system is comprised of BP Nanosheets (BPNSs) and a hydrogel (a hydrophilic network of polymer chains), and releases its cargo when exposed to a near-infrared light source. The black phosphorous photothermal transducing agents convert light to thermal energy, which increases the temperature of the hydrogel matrix. The agarose hydrogel then softens, which releases the drug from the black phosphorous scaffold into the body.
The process of softening is reversible, meaning the release can be controlled in bursts, so that the drug is discharged where it will be most effective. At the end of the treatment, enhanced laser power can be used to melt the hydrogel completely, degrading it into oligomers that are excreted through the urine.
Highly controllable drug release
The researchers loaded the hydrogel with Doxorubicin (DOX) – a commonly used cancer therapy – to measure the light-controlled drug release. When irradiated with a near-infrared source, the concentration of DOX increased dramatically compared with the control without irradiation. The researchers also showed that both light intensity and exposure duration accurately controlled the device.
Irradiation of 1 W·cm-1 applied to the BP@Hydrogel was sufficient for drug release. The temperature increase softens the device due to the hydrolysis of cross-linking. Complete melting occurs at 2 W·cm-1 irradiation, at which point the BPNSs are no longer encased by the hydrogel and degrade rapidly.
Safely degrades and shrinks tumours
The waste products were found to be non-toxic. Studies on mice found that tumours treated with a DOX-loaded BP@Hydrogel device, which were irradiated with an NIR light source, were notably smaller, demonstrating an excellent tumour ablation effect in vivo.
The BP@Hydrogel system can be loaded with other drugs to target a wide range of tumour types and other diseases, while minimizing unpleasant side effects. The authors believe a design such as this has the potential to help millions of patients suffering from cancer.
Full details are reported in the Proceedings of the National Association of Science 10.1073/pnas.171442111.