According to the World Health Organization, Colorectal Cancer (CRC) is the third most diagnosed malignancy and is the second leading cause of death among tumors worldwide. Conventional treatments include surgery, chemotherapy and radiotherapy, often accompanied by emerging immunotherapies, trying to reduce the burden of advanced and metastatic stages. Recently, nanomedicine therapies have been under intensive research to offer new perspectives to patients.
In this case study, we propose a treatment which combines the administration of nanoparticles and an external acoustic stimulus. In this way, we aim at a stimuli responsive and localized therapy, triggered by the safe use of acoustic shockwaves (SWs), a deep-penetrating tissue stimulation.
More in detail, the formulation of advanced biomimetic and targeted nanoparticles consists in iron-doped zinc oxide nanocrystals (ZnO-NPs), enveloped in a biomimetic lipid bilayer shell, which is further conjugated with a targeting peptide (YSA), enabling a selective targeting toward CRC cells.
On the other hand, the acoustic shockwaves are repeated and intense pressure impulses, produced by the PiezoWave (PW 2) device by Elvation Medical, which is already employed in clinics for treating muscle-skeletal diseases and was repurposed in this work for the combined treatment against CRC.
The combination of ZnO-NPs and SWs can produce a highly localized and efficient depletion of CRC, since the ZnO-NPs are engineered to preferentially be internalized by CRC cells, while the SWs can safely penetrate the human tissues, reaching the tumor mass. When the SWs hit the ZnO-NPs, they trigger the cytotoxic effect of the nanoparticles, achieving a synergistic malignant cell death.
Currently, we have performed numerous studies proving ZnO-NPs to be per se highly biocompatible, hemocompatible and non-toxic in both healthy and cancerous colorectal cells, as well as efficiently targeted toward the cells of interest while sparing the healthy counterpart. We also demonstrated that, both in 2D monolayer cell cultures and in 3D CRC models (spheroids, i.e., approximately 0.5 mm diameter self-organized spheres of malignant cells), the combined treatment of ZnO-NPs and SWs is able to synergistically damage malignant models leading to complete tumor mass ablation.
These findings pave the way for further pre-clinical and clinical validations of these remotely-controlled nanomedicine strategies. To learn more about our research and kept updated, see our publications about this topic: