Illustration of the functionalization of silica nanoparticles: detoxified biochemicals (SP-LPS) is attached to the nanoparticle, which is loaded with the anticancer drug doxorubicin (DOX).Drug-loaded nanoparticles that trick the immune system into responding could offer a new approach to cancer therapy, according to new research [Dong et al., Materials Today (2017), doi: 10.1016/j.mattod.2017.06.003].
Cancer cells exhibit higher levels of reactive oxygen species (ROS) than normal healthy cells and could provide a target for drug delivery systems. Other biological events also produce elevated ROS levels – such as the presence of harmful pathogens or lipopolysaccharides (LPS), which are found in the outer membrane of some bacteria.
So Jinsong Ren and Xiaogang Qu from Changchun Institute of Applied Chemistry and colleagues from the Chemical Biology Key Laboratory of Hebei Province and University of Chinese Academy of Sciences in Beijing designed a drug-loaded nanocomplex that mimics a pathogen to kick-start the body’s immune response to attack tumor cells.
The nanocomplex is based on silica nanoparticles 100 nm in diameter with large pores and high surface area. The nanoparticles are loaded with anticancer agents – in this case doxorubicin or rhodamine B – and functionalized with chemical species that respond to ROS. Finally, the drug-loaded nanoparticles are coated with detoxified LPS, which serves both to trap the drug inside the nanocarrier and elicit an immune response.
By mimicking a pathogen or bacterial threat, the nanocomplex is designed to trick the body into launching its immune response. Simultaneously, the overproduction of ROS at the tumor site opens the pores of the nanoparticle to release the anticancer drug.
The nanocomplex enables a combined chemotherapeutic/immunotherapeutic attack on the tumor. In cells, the researchers found that the nanocomplex produces a more pronounced reduction in the number of tumor cells than any of the elements of the system alone.
“By integrating the anti-tumor immune response and chemotherapy, the nanoparticle-based pathogen mimics exhibit a synergistic effect for cancer therapy,” says Jinsong Ren.
The results in mice are also promising, the researchers report. While the nanocomplex appears to be nontoxic and does not produce systemic inflammation, direct injection into cancerous tissue did have an effect.
“Importantly, chemotherapy and immunotherapy are acting in a synergistic manner to inhibit solid tumor growth,” explains Ren.
The researchers believe that the immune response produced by their pathogen-mimicking nanocomplex could also support the development of an immune system ‘memory’ of cancer antigens. Mice treated with the pathogen-mimicking nanoparticles demonstrated a lower rate of tumor recurrence than those treated with the anticancer drug alone, the researchers’ found.
“The novel pathogen-mimicking nanocomplex has the potential to open up new avenues for cancer therapy,” says Ren. “We plan to integrate targeting molecules into these nanocomplexes to enhance the outcome.”