Recent development of nanotechnology-based approaches for gynecologic cancer therapy

Gangaraju Gedda; Yoo-Jin Park; Myung-Geol Pang

doi:10.5468/ogs.24180

Obstet Gynecol Sci > Volume 68(1); 2025 > Article

Gedda, Park, and Pang: Recent development of nanotechnology-based approaches for gynecologic cancer therapy

Review Article

Gynecologic Oncology

Obstetrics & Gynecology Science 2025;68(1):18-29.

Published online: November 26, 2024

DOI: https://doi.org/10.5468/ogs.24180

Recent development of nanotechnology-based approaches for gynecologic cancer therapy

Gangaraju Gedda, PhD^1,^2,^*, Yoo-Jin Park, PhD^1,^*, Myung-Geol Pang, PhD¹

¹Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, Anseong, Korea

²Central Research Laboratory, KS Hegde Medical Academy, NITTE (Deemed to be University), Mangaluru, India

Corresponding author: Myung-Geol Pang, PhD Department of Animal Science & Technology and BET Research Institute, Chung-Ang University, 4726 Seodong-daero, Daedeokmyeon, Anseong 17546, Korea E-mail: mgpang@cau.ac.kr

^* These authors contributed equally to this work.

Received July 5, 2024 Revised September 29, 2024 Accepted November 13, 2024

Articles published in Obstet Gynecol Sci are open-access, distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Gynecological cancer is a life-threatening malignancy among women. Traditional therapies, including chemotherapy, often face challenges in terms of chemotherapeutic drug solubility and resistance, specificity, tumor site targeting, and toxicity to healthy tissues, leading to shortened efficacy and unfavorable patient outcomes and survival rates in patients with gynecologic malignancies. Recently, nanotechnology-based therapeutic methods such as targeted drug delivery and phototherapies have emerged as an appropriate alternative to overcome issues associated with traditional therapeutic methods. Specifically, nanomaterials and nanomaterial-based methods enhance the delivery of therapeutic/targeting agents to tumor sites and cellular uptakes and improve the tumor-suppressing effect. This review aims to provide an overview and future perspective on the potential impact of nanotechnology-based therapeutic methods for effective therapies for gynecologic cancer.

Keywords: Gynecology; Nanotechnology; Drug delivery system; Photodynamic therapy; Photothermal therapy

Introduction

Gynecologic cancers, such as ovarian, cervical, and endometrial cancers, are the most common cancers worldwide, accounting for more than 30% of all cancer-related deaths in women; however, the prognosis and diagnosis of these cancers remain poor [1,2]. Definitely, poor and delayed treatment is directly related to the development of malignancies and unfavorably affecting outcomes [3]. The 5-year survival rate of patients dramatically differed depending on the detection stages, that is, there is an approximately 90% survival rate during early stage endometrial cancer while less than 20% for the late stage [4,5]. An accurate and early diagnosis are required to reduce treatment burden for addressing morbidity and mortality. Clinically, the treatment of patients with cancer is a significant challenge owing to the close correlation between drug resistance and the progression of metastasis in distant organs and tissues, including mortality. Therefore, an in-depth understanding of the molecular mechanisms behind drug resistance in gynecologic cancers may shed light on the development of advanced treatment methods that address patients’ resistance phenomena.

Nanotechnology signifies an innovative footpath for technological advancement in science and technology using materials at the nano-scale [6-10]. Nanomaterials have been widely employed for sensors, diagnosis, and various treatments due to their unique properties such as water solubility, nano-size, high surface area, biocompatibility, bioavailability, low toxicity, high chemical and photostability, visibility to the near-infrared region (NIR) light absorption, and flexibility to surface modification [11-14]. Furthermore, nanomaterials-based therapeutic approaches in biomedicine emerged as a potential approach in developing more effective treatment methods to overcome the limitations associated with traditional methods. Researchers focus on developing and surface modification nanomaterials (liposomes, dendrimers, micelles, polymer, metal, metal oxide, silica, and carbon) with exceptional properties and functionalities [15,16]. Recently, nanosystem-based targeting drug delivery has been developed by integrating or incorporating therapeutics and targeting with nanomaterials to treat gynecologic cancer effectively [17-19]. They improve not only the drug solubility and specificity and target the delivery of drugs to the tumor site, but also enhance cell uptake and internalization of therapeutic agents, which leads to cell death. Moreover, photo-based therapies such as photodynamic and photothermal therapies can be employed by using integrated photosensitizer and NIR light-absorbing for chemotherapeutic drug-resistant gynecologic cancer treatments [20-22]. In this review, we initially discussed an overview of common mechanisms of gynecological drug resistance limitations. Next, we provided recent developments in various nanotechnology-based treatment methods, including targeted drug delivery and photothermal and photodynamic therapeutics for managing gynecological tumors. Finally, we elucidate the conclusion and future perspectives.

Mechanisms of drug resistance

Chemotherapy has been developed as a primary or adjuvant therapy integrated with cytoreductive surgery and radiation to treat patients with high-risk gynecologic cancers [23-26]. Despite the promising results of chemotherapy for managing tumor progression, recurrence is observed in 70% of patients with ovarian cancer within 2 years after cytoreductive surgery with chemotherapy, and approximately 50% of patients survive 5 years after being diagnosed with ovarian cancer [27,28]. Resistance to chemotherapy has been blamed as a major obstacle hindering cancer treatment, which leads to cancer relapse and death [28]. Drug resistance in gynecologic cancers indicates loss of susceptibility in tumors responding to chemotherapeutic treatments through the inhibition of tumor response to drugs [29]. Restriction of chemotherapy activity in tumor cells is classified into two categories, intrinsic and acquired, according to tumor response to the initial therapy [30]. Intrinsic drug resistance is considered when preexisting tumor cells are generated via unexpected genetic mutation and acquire survival ability against primary therapeutic treatment [31]. Otherwise, acquired resistance reduces drug sensitivity in tumors through the alteration of genetic, epigenetic, and tumor microenvironment systems following cancer treatment (Fig. 1) [32,33].

1. DNA strengthening following platinum-based chemotherapy

The platinum agents, cisplatin or carboplatin, are widely employed as the most effective drugs for ovarian cancer treatment, which induces cell apoptosis through the breakdown of DNA strands for impairment of DNA repair systems [28,34]. During initial platinum-based chemotherapy, ovarian cancer cells are very sensitive to drugs, which leads to impairment of the DNA repair system, resulting in apoptosis [35]. However, platinum-resistant tumor cells can evade the apoptotic program owing to the alterations in the DNA repair system, such as the deficiency of multiprotein-associated repair of mismatched DNA and functional restoration of homologous recombination repair by the reverse mutation of tumor suppressor genes, such as breast cancer type (BRCA) 1 and BRCA2 [36-38].

2. Changes in the drug transportation system

One of the major factors in platinum resistance is accompanied by inhibited drug accumulation in tumor cells through copper (Cu) transporters. Generally, copper homeostasis is maintained by balancing the influx of Cu uptake transporter (CTRL1) and efflux by an adenosine triphosphate copper transporter α (ATP7A) [39,40]. However, cisplatin induces internalization of CTRL1 from the plasma membrane, resulting in the loss of sensitivity of cancer cells to cisplatin [41]. Following the increase in intracellular Cu concentration, ATP7A is translocated from trans-Golgi to the plasma membrane to secrete Cu through the vesicular secretory pathway for minimizing the toxic effects from excessive Cu in cells [42]. Although ATP7A is a major mediator of Cu homeostasis in normal condition, overexpressed ATP7A leads to the platinum drug sequestration of platinum-based drugs in the vesicles, resulting in platinum-based medicine resistance and cross-resistance to Cu in ovarian cancers [42,43].

3. Detoxification of drugs

Although a higher level of reactive oxygen species (ROS) is observed in cancer cells compared to other cells, inordinate ROS generation by ionizing radiation and chemotherapy activates apoptosis signaling pathways in tumor cells [44]. However, tumor cells can evolve to prevent ROS damage by upregulating antioxidant enzymes, such as metallothionein (MT) and glutathione (GSH), following excessive ROS-induced cancer treatments [45-47]. GSH and MT protein containing thiol group bind to platinum-based drugs and form a complex with platinum-based drugs, which leads to the reduction of intracellular platinum concentration and results in drug inactivation, leading to drug resistance [47,48].

4. Epigenetic modifications

Developing drug-resistance in gynecologic cancers is accompanied by epigenetic modifications, such as DNA methylation, histone methylation/acetylation, and noncoding RNA interference [49,50]. Especially, cancer cell proliferation and anti-apoptosis activity is elevated by acceleration of mitogen-activated protein kinase, phosphoinositide 3-kinase/protein kinase B, and Wnt signaling pathways following epigenetic remodeling [51]. Moreover, histone modifications is closely related to chemotherapy resistance in ovarian cancer cells through gene silencing associated with chromatin stability [52]. Again, the development of resistance in cancer cells following chemotherapy is a major obstacle to cancer treatment. Regarding the side effects of anti-cancer drugs on normal tissues and multidrug-resistant tumors, new strategies using nanoparticles have been suggested to trigger apoptosis of drug-resistant cells through target-based delivery system [53,54].

Nanoparticle-based treatment for gynecological malignancies

Conventional therapeutic methods such as chemotherapy for the management of gynecological are limited by toxicity, poor selectivity and administration, low efficiency, and severe side effects [55]. Developments in nanotechnology-based targeted therapeutic approaches for gynecological cancer have witnessed substantial progress in overcoming the limitations of traditional methods and improving treatment efficiency [56-60]. Tumor targeting typically involves the incorporation of nanoparticles with targeting molecules, including ligands, antibodies, proteins, and peptides, on the surfaces of nanomaterials, owing to their significant affinity towards receptors that are overexpressed in gynecological cancers [61-66]. A modified nanocarrier with target molecules can identify and attach to receptors specific to cancer cells. Upon interaction with receptors on/in cancer cells, nanocarriers are internalized by receptor-mediated endocytosis. Consequently, the nanocarriers release their payloads such as chemotherapeutic agents, photosensitizers, or photothermal agents within cancer cells. The release may be triggered by the acidic environment of the endosomes or by light exposure. The administered therapeutic agents subsequently exhibit effects such as apoptotic induction, cellular proliferation inhibition, or immune response modification. This targeted strategy improves therapeutic efficacy while reducing adverse effects on healthy tissues. Here, we discuss recent developments in different nanomaterial-based targeted therapeutic approaches such as drug delivery, photothermal therapy, and photodynamic therapeutic methods for managing gynecologic cancer (Fig. 2).

1. Nanomaterial-assisted targeted drug delivery

Conventional pharmaceutical chemotherapeutics are typically distributed throughout the body, leading to unsatisfactory concentrations within malignancies. Nanomaterials can allow drug delivery by conjugating/encapsulating targeting agents and chemotherapeutic drugs accurately targeting cells or organs through sustainable release [67-69]. The large surface area, presence of many functional groups, and the hydrophilic/hydrophobic characteristics render them suitable host materials for the encapsulation and transport of different targeting and chemotherapeutic drugs [70-72]. Typically, the tumor cell-specific drug delivery is designed to sustain the release of drugs from the nano platform based on the physical conditions of the tumor site, such as pH [73,74]. The nanovehicle-based therapeutic drug delivery platform has abundant benefits, such as surface modification, water solubility, low toxicity, excellent biodegradability, biocompatibility, high drug loading capacity, bioavailability, stability, sustainable drug delivery, and improved therapeutic results compared to free drugs. They can also be suitable for delivering hydrophobic and hydrophilic drugs [68,75-78]. In this connection, several types of nanoparticles have been explored for their potential applications in gynecological cancer treatment.

Typically, the targeting nano vehicle system involves the delivery of the therapeutic agents to the specific target tumor site using targeting agents such as ligands, aptamers, antibodies, and peptides [79-84]. It enhances the drug internalization within cells and improves the therapeutic efficiency because the targeting agents attach with specific receptors overexpressed on tumor cells. For example, arginine-glycine-aspartic acid (RGD) peptides are able to attach to integrins, which are highly expressed proteins found on the surface of tumor cells including the endothelial cells located in tumor blood vessels. This binding improves treatment efficacy and minimizes negative effects by enabling the targeting and transport of therapeutic drugs directly to the tumor location. RGD peptide is a significant gynecological cancer-specific targeting ligand [85]. RGD-functionalized nanocargo can transport therapeutic drugs to the target tumor to support drug resistance treatment and improve therapeutic impact [86]. For example, Long et al. [87] reported a novel delivery system that conjugates RGD and resveratrol (natural ovarian cancer drug) to human serum albumin nanoparticles for targeting ovarian cancer therapy. The results showed that the RGD-modified nanocarrier system exhibited remarkably higher cellular updates than the RGD-unmodified nanocarrier system due to the specific targeting ability of integrins expressed in ovarian cancer. Similarly, Liang et al. [88], designed a targeting dual drug delivery nano-platform by integrating anticancer drugs such as cis-platin and olaparib simultaneously along with integer targeted ligand (cyclic RGD peptide) to heparin as a nanocarrier for ovarian cancer. Similarly, the folate receptor is highly expressed in endometrial, cervical, and ovarian cancers [89]. Thus, nanomaterials were functionalized with folic and therapeutic agents for selectively targeted systems for the local delivery of anti-cancer drugs against endometrial cancer. Changyan Liang et al. [90] exploited the folate-facilitated poly-lactide-co-glycolide-polyethylene glycol nanoparticles loaded with paclitaxel for targeting endometrial cancer. The results revealed that the prepared folate-mediated nanomaterials had improved the targeting specificity and efficiency towards the tumor site, and it revealed a significant anticancer effect compared to the paclitaxel drug alone. Analogously, antibody-based nanosystems represent a promising development in tailored delivery of drugs for the treatment of gynecological cancer. By combining the adaptability of nanoparticles with the specificity of antibodies, drugs are delivered specifically to cancer cells with a minimum negative impact on healthy cells. Antibodies are engineered to identify and attach to particular antigens present on the surface of cancer cells. This ensures the accurate delivery of drug-loaded nanoparticles to the tumor location. Upon binding to the cancer cell, the nanoparticle can deliver its medicinal payload straight into the cell, thereby boosting the therapeutic benefit and minimizing adverse effects. The vascular endothelial growth factor (VEGF) and its receptor are overexpressed cervical cancers. Therefore, anti-VEGF antibodies such as bevacizumab incorporated with therapeutic agent-modified nanomaterials were established to manage cervical cancer. Dana et al. [91] developed cisplatin-loaded poly lactic-co-glycolic acid-liposome nanocomposite with an anti-VEGF antibody as a targeting agent for specific cervical cancer therapy. The prepared anti-VEGF antibody-modified nanocomposite increased cisplatin therapeutic effectiveness via molecular directing. On the other hand, mitochondria are recognized as an innovative target in managing gynecological cancer. Oladimeji et al. [92] loaded paclitaxel (anticancer drug), epigallocatechin gallate (laminin receptor overexpressed in most cancers), and triphenyl phosphonium cation (mitochondrial directing agent) into co-polymers such as poly-D-lysine and polyethene glycol grafted gold nanomaterials for mitochondrial targeting delivery potentiality of paclitaxel in cervical carcinoma tumor. Mitochondrial targeting is conducted to specifically localize mitochondrial cancer cells and demonstrate the potent effect of subcellular targeting, particularly to the mitochondria in tumors, as progress in the therapeutic effect on cervical carcinoma. Thus, targeting agent-modified nanosystems is an effective method for specific cells targeting the delivery of anti-cancer drugs to improve the therapeutic efficiency against gynecological cancer.

2. Nanomaterial-assisted photothermal therapy (PTT)

Nanomaterial-based PTT is a relatively advanced and newly developed therapeutic modality for effectively treating gynecologic cancer. PTT gained significant attention owing to its non-invasive, spatial and temporal selectivity, precise targeting, and minimal damage to normal cells [93-95]. PTT utilized photo-absorbing photothermal agents to produce significant localized heat under NIR light to increase the temperature of surrounding tissues and trigger cancer cell death [96,97]. During PTT, photothermal agents are exposed by laser at a precise NIR wavelength to induce localized heat, leading to denaturation of protein, cellular membrane eradication, and DNA destruction, resulting in selective tumor tissue ablation. Furthermore, external laser irradiation with an adjustable dosage allows the selective elimination of gynecologic cancer and minimizes injury to the surrounding normal cells. The therapeutic efficacy of PTT mainly depends on altering light to satisfactory heat energy with photothermal agents, especially nanomaterial-based PTT agents. Accordingly, various nanomaterials, such as metal, carbon, lipid, and polymer-based nanomaterials, are investigated for the photothermal ablation of gynecological cancer [20,98]. For example, Zhang et al. [98] synthesized highly stable and biocompatible polyethylene glycol (PEG) polymer-grafted gold (Au) nanorods for effective photothermal treatment of cervical cancer. The results reveal that, upon 793 nm NIR laser (793 nm) irradiation, PEG-modified Au nanorods (NRs) nanorods effectively convert photon energy into localized heat, leading to significant HeLa cancer cell death. Meanwhile, it shows decreased toxicity towards normal cells. Thus, highly biocompatible Au-PEG NRs offer an efficient nano platform for cervical cancer via photothermal ablation. Zhang et al. [99] loaded indocyanine green into polydopamine functionalized magnetic nanomaterials for laser-induced photothermal ablation of cervical cancer. The results showed that functionalized magnetic nanomaterial induced 54.1°C heat and photothermal conversion efficacy of 35.21% under 793-nm laser exposure for 10 minutes with a power density at 0.33 W/cm². Moreover, toxicity studies found that nanomaterials (absence of laser) treated with HeLa cells showed lower toxicity (90% survival rate). Under laser irradiation, the photothermal ability of the nanomaterials on HeLa cells reached 81.81%. Similarly, Zhong Du developed an incorporation of PEG-encapsulated polydopamine nanomaterials to improve photothermal therapy for cervical cancer. The prepared nanomaterials exhibited an increased photothermal conversion efficiency of approximately 43.7% under 808-nm laser irradiation [100]. Yu et al. [101] discovered the feasibility of carbon-covered molybdenum selenide (C-MoSe) nanomaterials as near-infrared nano absorbers for photothermal therapy against ovarian cancer. The results indicated that the prepared C-MoSe nanomaterials revealed the lowest cell viability, that is, 61.6%, and an apoptosis rate of nearly 43.24%, and simultaneously raised intracellular ROS level by approximately 93.86%. C-MoSe had no noticeable toxicity towards normal cells or healthy tissues. Similarly, various types of nanomaterials such as Ag@Fe₃O₄ nanoparticles [102], biodegradable conjugated polymers [103] and Fe₃O₄-PEG nanoparticles [104], and CuS-MnS2 nano-flowers [105] were employed as NIR laser-absorbing photothermal agents for the management of ovarian cancer. Besides this, NIR laser-absorbing nanomaterials are reported for photothermal therapy to treat endometriosis. Moses et al. [106] grafted silicon phthalocyanine (SiNc) on polymeric silicon naphthalocyanine nanoparticles (SiNc-NPs) for photothermal therapy for endometriosis. The results exhibited that SiNc-NPs had a more than 95% of endometriotic cell death at 780-nm NIR light for 15 minutes. Also, SiNc-NP completely eradicated the endometriotic tissues without any side effects. Therefore, these results demonstrated that SiNc-NPs are effective nanophotothermal agents for the treatment of endometriosis. Hydrogel [107,108] and gold nanosphere [109] are also used for endometriosis treatment via PTT. NIR light-absorbing nanomaterial-based PPT treatment methods showed high absorption efficiency, effective alteration of light into heat, high photothermal conversion efficiency, and negligible toxicity.

3. Nanomaterial-assisted photodynamic therapy

Photodynamic therapy is a minimally invasive treatment that uses specific wavelength light energy, cellular oxygen, and light-activated compounds such as photosensitizing agents for gynecological cancer therapy [110]. In photodynamic therapy (PDT) treatment, the cells were treated with photosensitizers and exposed to specific wavelengths. The light-activated photosensitizer interacts with molecular oxygen and generates ROS, including singlet oxygen, superoxide, and hydroxyl radicals [111,112]. ROS initiaes oxidation damage and cell death via apoptosis (programmed cell death) or necrosis. PDT offers superior specificity against tumor cells and lower toxicity than traditional therapeutic methods. PDT limits destruction of normal cells as the photosensitizing agents tend to accumulate in tumor cells, and the light is exposed directly to them. Although traditional organic photosensitizers have achieved remarkable progress in PDT, the shortcomings include low stability and hydrophobicity. Nano-based PDT systems are developed to manage gynecology cancer treatment [20,113,114]. The nanomaterials facilitate the specific delivery of photosensitizers toward the tumor location and increase cellular uptake owing to the higher surface area and multipurpose surface alterations. In this connection, various kinds of nanomaterials, such as metal, metal oxide, polymers, and carbon-based nanomaterials, are established for PDT of gynecological cancer [20,115,116]. Tan et al. [117] demonstrated the PDT effect of pyro-pheophorbide (photosensitizer) encapsulating into Fe₃O₄@SiO₂ nanomaterials against ovarian cancer cells. The results found that nanomaterials are internalized with call and exhibited a lower toxicity without laser exposure; however, outstanding phototoxicity was observed under a 675-nm laser exposure at a power density of 5 mW/cm² for 30 minutes. Generating high-level singlet oxygen played a vital role in cell death. In the meantime, nanomaterials displayed good biocompatibility and low toxicity towards normal cells such as mouse normal fibroblast cell lines (L929 cells). Similarly, curcumin-incorporated biodegradable polymeric [118], molybdenum-iodide nanocluster-loaded PEGylated poly (lactic-co-glycolic acid) PEGylated poly (lactic-co-glycolic acid) nanocomposite [119], benzoporphyrin incorporated nanolipid [120], and verteporfin-encapsulated lipid [121] nanomaterials were employed for the PDT treatment of ovarian cancer. Nanomaterial-assisted PDT was also successfully applied for the treatment of cervical cancer. Gulinigaer Alimu et al. [122] loaded methylene blue (MB) and Chlorin e6 (Ce6) photosensitizers into lipid (Ce6-MB@Lips) nanomaterials for boosted photodynamic therapy of cervical cancer. The prepared Ce6-MB@Lips showed high stability, ¹O₂-generation potentiality, cellular uptake phototoxicity, and lower toxicity to normal cells than tumor cells. Under 660-nm laser irradiation, Ce6-MB@Lips generate more ROS in the tumor cells for effectually inducing apoptosis of HeLa (apoptosis rate 78.35%) and SiHa cells (apoptosis rate 68.45%). Nanomaterial-assisted PDT promotes progress in the anti-gynecology tumor effect by generating ROS, such as singlet oxygen under specific laser wavelength.

Conclusion

The advancement of nanotechnology and nanomedicine has opened new windows for the precise and efficient treatment for managing gynecology cancers, including ovarian, cervical, and endometrial malignancies. Typically, nanotechnology depends on utilizing nano-scale materials, which would resolve the limitations of traditional therapies, such as improving chemotherapeutic drug solubility and target specificity due to their distinct properties. Nanomaterials transport therapeutic and targeting agents to specific tissues and improve cellular uptake and internalization due to their nano size, unique sizes, high surface area, and physicochemical properties. Surface modification on nanoparticles can enhance the specificity and cellular uptake of cancers and help treat gynecology cancers accurately. The foremost concern about using nanomaterials in the biomedical area is associated with their preparation, water solubility, toxicity, bioavailability, and biocompatibility. Some nano-scale materials, such as quantum dots, metal-based nanocarriers and carbon nanotubes, are not biodegradable. On the other hand, liposomes and polymer-based material preparation involve either complicated preparation processes or purification approaches, which restricts their use in in vivo therapy. Moreover, scaling up preparations of nanomaterials for biomedical applications is critical. Thus, it is imperative to develop economical, ecofriendly, and green approaches to the large-scale preparation of nanomaterials. Additional issues that need to be addressed should highlight on developing nanomaterials rather than the disease. For example, most of the development of nanomaterial-based treatments focused on ovarian and cervical cancer but was limited to other gynecology cancers. Additionally, the investigation of nanomaterial interaction with gynecologic cancer cells and their molecular and pathological mechanisms remains limited.

Notes

Conflict of interest

All authors declare that there is no conflict of interest.

Ethical approval

Not applicable.

Patient consent

Not applicable.

Funding information

This work was supported by the Brain Pool Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (grant number: RS-2023-00236822), and by the Basic Science Research Program through the National Research Foundation of Korea (NRF), supported by the Ministry of Education (NRF-2018R1A6A1A03025159).

Fig. 1.

Mechanisms of chemoresistance in ovarian cancer cells (created with BioRender.com). GSH, glutathione.

Fig. 2.

Schematic illustration of nanotechnology treatment methods for gynecologic cancers (created with BioRender.com). ROS, reactive oxygen species.

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