Synergistic Phenomena between Iron-Doped ZnO Nanoparticles and Shock Waves Exploited against Pancreatic Cancer Cells

Abstract

We propose the use of iron-doped zinc oxide nanoparticles (Fe:ZnO NPs) showing theranostic capabilities and being synergistically active against pancreatic ductal adenocarcinoma once combined with mechanical pressure waves, such as shock waves. Fe:ZnO NPs are synthesized by employing oleic acid as a capping agent and are functionalized with amino-propyl groups. We first report their superior characteristics with respect to undoped ZnO NPs in terms of magnetic properties, colloidal stability, cytocompatibility, and internalization into BxPC-3 pancreatic cancer cells in vitro. These Fe:ZnO NPs are also cytocompatible toward normal pancreatic cells. We then perform a synergistic cell treatment with both shock waves and Fe:ZnO NPs once internalized into cells. We also evaluate the contribution to the synergistic activity of the NPs located in the extracellular space. Results show that both NPs and shock waves, when administered separately, are safe to cells, while their combination provokes an enhanced cell death after 24 h. Various mechanisms are then considered, such as dissolution of NPs, production of free radicals, and cell membrane disruption or permeation. It is understood so far that iron-doped ZnO NPs can degrade intracellularly into zinc cations, while the use of shock waves produce cell membrane permeabilization and possible rupture. In contrast, the production of reactive oxygen species is here ruled out. The provoked cell death can be recognized in both apoptotic and necrotic events. The proposed work is thus a first proof-of-concept study enabling promising future applications to deep-seated tumors such as pancreatic cancer, which is still an unmet clinical need with a tremendous death rate.

Lipidic Formulations Inspired by COVID Vaccines as Smart Coatings to Enhance Nanoparticle-Based Cancer Therapy

“…As a proof of concept, these lipid-coated NPs were tested against a pancreatic cancer cell line (BxPC-3) to show their increased biostability and biocompatibility compared to uncoated nanoparticles. The nanoparticles at the core of the nanoconstructs, designed and already applied in previous works [28,29], are zinc oxide NPs doped with iron, whose effect has been extensively shown to increase the tolerability and decrease the dissolution of the NPs in biological systems [30,31].…”

Anti-CD38 targeted nanotrojan horses stimulated by acoustic waves as therapeutic nanotools selectively against Burkitt’s lymphoma cells

“…The high tissue-penetrating capability of US [ 9 ] can be exploited in synergy with safe-by-design nanoparticles to achieve on demand and localized cytotoxic effects for the eradication of tumors. The exposure of NPs to US irradiation produces the enhanced occurrence of different phenomena, as photon emission [ 10 ], advantageous for imaging purposes, ROS generation [ 11 , 12 ] and microjets formation [ 11 , 13 , 14 ] able to create physico-chemical damages to tumoral cells, leading to cells apoptosis or necrosis and constructing an effective theranostic tool. Recently Zinc oxide nanocrystals (ZnO NCs) has been proposed as effective sonosensitizing nanoparticles, able to produce dramatic effect when applied in combination with ultrasound [ 11 ] or shock waves [ 13 ] to different types of cancer cells [ 14 , 15 ], yet producing ROS, zinc cation release and mechanical damages.…”

“…The exposure of NPs to US irradiation produces the enhanced occurrence of different phenomena, as photon emission [ 10 ], advantageous for imaging purposes, ROS generation [ 11 , 12 ] and microjets formation [ 11 , 13 , 14 ] able to create physico-chemical damages to tumoral cells, leading to cells apoptosis or necrosis and constructing an effective theranostic tool. Recently Zinc oxide nanocrystals (ZnO NCs) has been proposed as effective sonosensitizing nanoparticles, able to produce dramatic effect when applied in combination with ultrasound [ 11 ] or shock waves [ 13 ] to different types of cancer cells [ 14 , 15 ], yet producing ROS, zinc cation release and mechanical damages. Actually, zinc oxide nanoparticles are among the most promising materials for theranostic applications [ 14 , 16 ] due to their wide band gap [ 17 ], suitable for optical imaging, their high surface reactivity, and their response to ultrasound irradiation [ 10 , 11 , 13 , 18 ] leading to the above mentioned physico-chemical damages to cells.…”

“…Recently Zinc oxide nanocrystals (ZnO NCs) has been proposed as effective sonosensitizing nanoparticles, able to produce dramatic effect when applied in combination with ultrasound [ 11 ] or shock waves [ 13 ] to different types of cancer cells [ 14 , 15 ], yet producing ROS, zinc cation release and mechanical damages. Actually, zinc oxide nanoparticles are among the most promising materials for theranostic applications [ 14 , 16 ] due to their wide band gap [ 17 ], suitable for optical imaging, their high surface reactivity, and their response to ultrasound irradiation [ 10 , 11 , 13 , 18 ] leading to the above mentioned physico-chemical damages to cells. Furthermore, ZnO has been proven to be selectively toxic per se against cancer cells [ 16 , 19 ] and more tolerated by healthy ones.…”