###### Abstract  
Cisplatin, a representative anticancer drug used to treat cancer, has many adverse effects. In particular, it causes significant damage to the kidneys. Thus, many researchers have studied the delivery of drugs, such as cisplatin, to cancer areas using targeted drug-delivery systems. Here, we propose a new way to treat cancer by delivering anticancer drugs directly to the tumor site using the electrospray (ES) technique. We determined the optimal conditions for ES to promote the introduction of cisplatin into cancer cells. In our results, the group with cisplatin delivery-based electrospray (CDES) at 6 kV had an apoptosis of cancer cells approximately two times more than the group treated with cisplatin alone. We also confirmed that ES alone did not affect the survival of cells up to a voltage of 6 kV, but increased the permeability of the cell plasma membrane instantaneously, facilitating the influx of the drug. electrospray; anticancer treatment; cisplatin; drug delivery; cancer +
Footnote †: journal: Medical Biology  
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Footnote 1: email: _Applied_  
Footnote †: journal: Medical Biology  
if anticancer drugs can be used to treat locally at a tumor site, the side effects could be minimized, and the treatment effectiveness could be increased [8; 9; 10; 11; 12; 13; 14]. Cisplatin, which contains two chlorine atoms and ammonia in platinum atoms, is the most representative anticancer drug used to treat a number of cancers [15]. Cisplatin, which binds DNA, can inhibit the replication of cancer cells. Generally, this drug is administered via an injection. Thus, there are many side effects, such as a large impact on the kidneys [16; 17]. Many researchers continue to study cisplatin or other drug delivery systems to improve efficiency and thus reduce these side effects. For example, by decorating biomarkers and magnetic materials to nanocarriers, loaded drugs were delivered to only the cancer site [18; 19; 20; 21; 22]. Additionally, the drug was injected directly into the tumor mass [23], hyperthermia was applied in the target area to induce rapid movement of the drug [24; 25], or electroporation was used to accelerate the absorption of the drug into the cancer tissue [26; 27; 28]. Electrospray (ES) techniques provide micro- or nano-sized and charged droplets. This approach is generally used to manufacture nanoparticles and to encapsulate drugs or cells in polymers [29; 30; 31; 32; 33]. However, [PERSON] et al. proposed that an electrospray method can be used to introduce genes into cells [34]. Subsequently, several research teams used this technique to transfer external materials into cells [35; 36]. These studies showed that applying an electrical field by electrospray can facilitate the delivery of exogenous materials, making the ES technique a novel physical drug delivery system without severe damage, similar to traditional electroporation methods, because the delivery is mainly done by the impact of droplets on the cell surface [34]. Our research team also reported previous studies that applied this technique to transfer genes into cells [37]. By applying an appropriate voltage, this technology can promote the influx of external substances while minimizing the impact on cells. In this study, we endeavored to develop a novel cisplatin delivery-based electrospray (CDES) system for cancer cell lines, proposed a new method for inducing apoptosis of cancer cells by delivering cisplatin using an electrospray method and indirectly proved the mechanism. Figure 1 shows a schematic of the CDES system. All the system facilities were installed on a clean bench. The syringe tip and the ground of the ring shape were connected to a high-voltage generator. Phosphate-buffered saline (PBS) was used as the electrospray solution, as was done in our previous study. Initially, to confirm how much damage was caused to cells by ES, cell viability was measured after treatment with ES at various voltages.