Drug-loaded piezoelectric polymer nanoparticles can cross the blood-brain barrier to deliver anticancer drugs and electrical stimulation to tumor cells in the brain.
Drug-loaded piezoelectric polymer nanoparticles can cross the blood-brain barrier to deliver anticancer drugs and electrical stimulation to tumor cells in the brain.

Researchers have developed new nanoparticles for the treatment of glioblastoma, one of the most aggressive, invasive, and difficult to treat brain cancers [Pucci et al., Acta Biomaterialia (2021), https://doi.org/10.1016/j.actbio.2021.04.005 ].

“Glioblastoma cells are highly aggressive and require multi-modality treatments,” explains Gianni Ciofani of the Istituto Italiano di Tecnologia for Smart Bio-Interfaces, who led the work. “[This] aggressiveness is associated with the ability [of glioblastoma cells] to invade brain tissue, so it is important to inhibit their motility, invasiveness, and proliferation to avoid progression.”

Together with colleagues from the IRCCS Istituto Giannina Gaslini, University of Florence, European Laboratory for Non-linear Spectroscopy, and Istituto Italiano di Tecnologia for Electron Microscopy, Ciofani has developed nanoparticles composed of a piezoelectric polymeric core, into which drugs can be encapsulated, and a lipid shell that is highly biocompatible.

“The delivery of a drug or a drug-loaded nanomaterial [to the brain] represents a huge challenge because of the presence of the blood-brain barrier (BBB), a biological barrier that protects the brain by preventing the passage of toxic compounds and microorganisms,” says Ciofani. “It is difficult to deliver chemotherapy drugs from blood capillaries to brain tumors [so] drugs cannot be used in high concentrations because of their strong side effects on healthy tissue.”

To overcome this problem, the researchers functionalized the nanoparticles’ surface with a peptide known to facilitate the movement of chemical species through the BBB. Using a biomimetic microfluidic model of the BBB, the researchers demonstrate that the novel nanoparticles can indeed pass through the barrier. Once in the brain, the same peptide helps the nanoparticles target tumor cells and deliver a double blow. When stimulated with ultrasound, the piezoelectric nanoparticles not only release their drug cargo but also produce an electrical signal in response to the mechanical deformation.

“Since electrical stimuli are known to induce the inhibition of cell proliferation and the reduction of chemotherapy resistance, we have used [piezoelectric nanoparticles] to deliver anticancer electrical cues to glioblastoma cells,” says Ciofani.

The nanoparticles offer a potential multimodal treatment of glioblastoma, delivering both anticancer drugs in a controlled manner to kill cancer cells while minimizing effects on healthy tissue and electrical stimulation to inhibit cell mobility.

“The combined piezoelectrical stimulation and chemotherapy treatment was able to induce glioblastoma cell death, inhibit cell division, and reduce both glioblastoma cell invasiveness and epithelial-mesenchymal transition, [which is] associated with glioblastoma progression,” says Ciofani. “These polymeric nanomaterials display a high potential for approval in clinical applications.”

The approach could provide on-demand, non-invasive, and more efficacious anticancer treatment in highly sensitive areas like the brain, improving outcomes for patients, which are currently very poor.