**1. Introduction**

Emerging clinical evidence indicates OC is a disease associated with poor survival and high mortality and the current situation of OC oncotherapy has created a major problem for the health system [1, 2]. Due to the limited therapeutic results of conventional modalities, the majority of efforts in OC treatment studies focus on new therapeutic strategy achievement. The new perspectives for OC management should not have been unwanted side effects such as drug resistance and toxicity [3, 4]. Nanotechnology and gas plasma offering a promising alternative to conventional OC therapies [5–7].

Nanotechnology uses nanomaterial for a wide range of various purposes including biomedicine, energy, electronics, environment, food, and textile. Nanoparticles (NPs) have been engineered from various materials with unique properties as drug

### **Figure 1.**

*Schematic illustrating of all reviewed treatment modalities for OC oncotherapy. DDS (drug delivery system), GDS (gene delivery system), CAP (cold atmospheric plasma), PAL (plasma activated liquid), CTX (chemotherapy).*

vehicles to treat a peculiar disease [8–10]. Cancer nanomedicine creates a suitable strategy for modern oncotherapy and has attracted a lot of attention in recent years. The therapeutic nature of nanoparticles, drug delivery, and gene delivery are important foundations for increased attention to this new field [10–12].

The gas plasma that generates through conducting noble gas to the paired electrode at room temperature offers a new category of oncotherapy strategy in a short time [13]. Gas plasma oncotherapy will become an option for cancer treatment shortly, given its fast-development and multifunctional nature. This technology has provided the link between multidisciplinary scientific areas including physics, chemistry, biology, and medicine to address problems and offers an effective route for various oncotherapy challenges [14–16]. Multiple physical and chemical agents including charged particles, electric fields, ultraviolet (UV) radiation, and reactive oxygen and nitrogen species (RONS) involved in the efficacy of gas plasma [15].

NPs and gas plasma have risen as a promising therapeutic option for the treatment of ovarian malignant. These technologies exhibit comparable selectivity against tumor cells and provide a more efficacious and safe option for OC oncotherapy. The literature has been shown that NPs and gas plasma remarkably enhance the delivery of anticancer drugs and improve the efficacy of treatment and minimize the adverse effects of chemotherapeutic agents in healthy cells [16, 17].

This chapter presents the antitumor effect of gas plasma in combination with nanoparticle-based technology, as a new and most promising multimodal cancer therapy (**Figure 1**). Here, we provide a comprehensive and prospective review of the application of novel plasma and nanotechnology for the combination or multimodal OC oncotherapy.

## **2. Ovarian cancer: conventional treatment and resistance to chemotherapy**

OC is one of the most common gynecological malignancies throughout the world and the fifth leading cause of cancer-related deaths among women in the

**177**

*Nano Technology and Gas Plasma as Novel Therapeutic Strategies for Ovarian Cancer…*

acquired drug resistance of the tumor after a time duration [19].

United States [18]. According to the American Cancer Society statistics, it was estimated that there would be 22,530 women who will receive a new diagnosis of OC and about 13,980 women will die from the disease in 2019. Carboplatin and platinum-based chemotherapy were used as the first choice to treat this type of cancer. Findings indicate who patients respond well to the initial treatment regime

The main mechanisms of carboplatin resistance include reducing drug accumulation by altering the uptake/flow index, inactivating cisplatin by increasing the level of intracellular thiols such as glutathione, metallothionein, or other sulfur-containing molecules, increasing the repair capacity of platinum-induced DNA damage at the total level. The genome and DNA sequence become specific and the failure of the apoptotic response. Increasing the delivery of platinum to the tumor, a combination of platinum drugs with targeted molecular agents, modulators of platinum resistance, and new platinum drugs that target resistance mechanisms are the most important strategies being pursued that after intensive studies by many researchers are working to circumvent the resistance of cisplatin

Mortality trends in OC show the inefficiency of current therapeutics modalities except for PARPi and anti-VEGF. Thus, it is urgent to explore novel and efficient therapeutic options for epithelial OC that have the most lethal world gynecologic

Nanotechnology as a science for minimizing material with particular properties has been used in various fields and multidisciplinary sciences such as chemistry, biology and physic. NPs in medicine application is called nanomedicine and it is utilized for the profit of human health and well being. In the field of nanomedicine, NPs in diagnosis, pharmacological treatment at a molecular level, molecular imaging, tissue engineering and regenerative medicine are widely used [9, 12, 22]. Agents through surface interaction, encapsulation, or entrapping loaded into NPs, and based on their properties avail for active and passive drug delivery. NPs based on their diverse structure like branched, spherical, or shell shape offer to become suitable for drug delivery to specific diseases such as cancer. Conventional chemotherapy distributes in the whole body and destroys both normal and tumor cells, as well as, after a while cancer cells become resistant to drugs [11, 23].

Controlling drug delivery and accumulation in tumor cells caused to require lower drug concentration for improving oncotherapy and diminishing the side effect for normal cells. Released agents from NPs are controlled by external or internal stimuli like pH, electric or magnetic field, temperature, redox and sound,

The optimal nano-size range for increase efficiency is typically 1-100 nm. There are different types of NPs for instance polymeric NPs, quantum dots, lipid-based NPs, mesoporous silica and dendrimers. Biodistribution, circulation time, stability, bioavailability, size, shape and surface charge are common characteristics of NPs

For experimental and clinical trials, preparing an NP requires attention to some properties for better quality. Cellular recognition by specific antibodies is necessary for target delivery to specific cells [26]. NPs shouldn't stimulate the immune system

**3. Nanotechnology as a therapeutic option for ovarian cancer**

*DOI: http://dx.doi.org/10.5772/intechopen.96387*

and carboplatin [20, 21].

malignancy.

**3.1 Nanoparticles**

and it ameliorates target therapy [24].

that play an important role in their functioning [25].

to prevent degradation of them and their agents [27].

*Nano Technology and Gas Plasma as Novel Therapeutic Strategies for Ovarian Cancer… DOI: http://dx.doi.org/10.5772/intechopen.96387*

United States [18]. According to the American Cancer Society statistics, it was estimated that there would be 22,530 women who will receive a new diagnosis of OC and about 13,980 women will die from the disease in 2019. Carboplatin and platinum-based chemotherapy were used as the first choice to treat this type of cancer. Findings indicate who patients respond well to the initial treatment regime acquired drug resistance of the tumor after a time duration [19].

The main mechanisms of carboplatin resistance include reducing drug accumulation by altering the uptake/flow index, inactivating cisplatin by increasing the level of intracellular thiols such as glutathione, metallothionein, or other sulfur-containing molecules, increasing the repair capacity of platinum-induced DNA damage at the total level. The genome and DNA sequence become specific and the failure of the apoptotic response. Increasing the delivery of platinum to the tumor, a combination of platinum drugs with targeted molecular agents, modulators of platinum resistance, and new platinum drugs that target resistance mechanisms are the most important strategies being pursued that after intensive studies by many researchers are working to circumvent the resistance of cisplatin and carboplatin [20, 21].

Mortality trends in OC show the inefficiency of current therapeutics modalities except for PARPi and anti-VEGF. Thus, it is urgent to explore novel and efficient therapeutic options for epithelial OC that have the most lethal world gynecologic malignancy.

### **3. Nanotechnology as a therapeutic option for ovarian cancer**

### **3.1 Nanoparticles**

*Ovarian Cancer - Updates in Tumour Biology and Therapeutics*

vehicles to treat a peculiar disease [8–10]. Cancer nanomedicine creates a suitable strategy for modern oncotherapy and has attracted a lot of attention in recent years. The therapeutic nature of nanoparticles, drug delivery, and gene delivery are

*Schematic illustrating of all reviewed treatment modalities for OC oncotherapy. DDS (drug delivery system), GDS (gene delivery system), CAP (cold atmospheric plasma), PAL (plasma activated liquid), CTX* 

The gas plasma that generates through conducting noble gas to the paired electrode at room temperature offers a new category of oncotherapy strategy in a short time [13]. Gas plasma oncotherapy will become an option for cancer treatment shortly, given its fast-development and multifunctional nature. This technology has provided the link between multidisciplinary scientific areas including physics, chemistry, biology, and medicine to address problems and offers an effective route for various oncotherapy challenges [14–16]. Multiple physical and chemical agents including charged particles, electric fields, ultraviolet (UV) radiation, and reactive oxygen and nitrogen species (RONS) involved in the efficacy of gas plasma [15]. NPs and gas plasma have risen as a promising therapeutic option for the treatment of ovarian malignant. These technologies exhibit comparable selectivity against tumor cells and provide a more efficacious and safe option for OC oncotherapy. The literature has been shown that NPs and gas plasma remarkably enhance the delivery of anticancer drugs and improve the efficacy of treatment and minimize

important foundations for increased attention to this new field [10–12].

the adverse effects of chemotherapeutic agents in healthy cells [16, 17].

**2. Ovarian cancer: conventional treatment and resistance to** 

This chapter presents the antitumor effect of gas plasma in combination with nanoparticle-based technology, as a new and most promising multimodal cancer therapy (**Figure 1**). Here, we provide a comprehensive and prospective review of the application of novel plasma and nanotechnology for the combination or multi-

OC is one of the most common gynecological malignancies throughout the world and the fifth leading cause of cancer-related deaths among women in the

**176**

**Figure 1.**

*(chemotherapy).*

modal OC oncotherapy.

**chemotherapy**

Nanotechnology as a science for minimizing material with particular properties has been used in various fields and multidisciplinary sciences such as chemistry, biology and physic. NPs in medicine application is called nanomedicine and it is utilized for the profit of human health and well being. In the field of nanomedicine, NPs in diagnosis, pharmacological treatment at a molecular level, molecular imaging, tissue engineering and regenerative medicine are widely used [9, 12, 22].

Agents through surface interaction, encapsulation, or entrapping loaded into NPs, and based on their properties avail for active and passive drug delivery. NPs based on their diverse structure like branched, spherical, or shell shape offer to become suitable for drug delivery to specific diseases such as cancer. Conventional chemotherapy distributes in the whole body and destroys both normal and tumor cells, as well as, after a while cancer cells become resistant to drugs [11, 23].

Controlling drug delivery and accumulation in tumor cells caused to require lower drug concentration for improving oncotherapy and diminishing the side effect for normal cells. Released agents from NPs are controlled by external or internal stimuli like pH, electric or magnetic field, temperature, redox and sound, and it ameliorates target therapy [24].

The optimal nano-size range for increase efficiency is typically 1-100 nm. There are different types of NPs for instance polymeric NPs, quantum dots, lipid-based NPs, mesoporous silica and dendrimers. Biodistribution, circulation time, stability, bioavailability, size, shape and surface charge are common characteristics of NPs that play an important role in their functioning [25].

For experimental and clinical trials, preparing an NP requires attention to some properties for better quality. Cellular recognition by specific antibodies is necessary for target delivery to specific cells [26]. NPs shouldn't stimulate the immune system to prevent degradation of them and their agents [27].

In gen delivery NPs carrying nucleic acids containing microRNA (miRNA), short hairpin RNA (shRNA), antisense oligonucleotides (AONS) and small interfering RNA (siRNA), with the silencing or downregulation purpose of genes or proteins which related to drug-resistant, angiogenesis or metastasis are used for improving oncotherapy and resolve the conventional therapy limitation [28]. We summarize nanotechnology based therapeutics in **Figure 2**. Here, we review the pre-clinical application of NPs for OC oncotherapy.
