Introduction: Ovarian cancer is one of the most lethal malignancies of the female reproductive system, primarily due to late diagnosis and the development of drug resistance, which continue to pose major challenges in treatment. Conventional therapeutic approaches, such as surgery and chemotherapy, often show limited efficacy and are associated with severe side effects. In recent years, growing attention has been directed toward nanotechnology and novel drug delivery systems. Biocompatible nanoparticles such as zein and sodium caseinate, owing to their drug-loading capacity, stability, and controlled release properties, have opened new and promising perspectives in ovarian cancer therapy. This review article discusses the underlying biological mechanisms of ovarian cancer, highlights the role of key genes and molecular pathways, and explores recent advances in the application of protein-based nanoparticles for treatment. Finally, the limitations and future opportunities of this field are also addressed.
Methods: Approximately 10% of ovarian cancer cases are hereditary, most commonly associated with mutations in the BRCA1 and BRCA2 genes, which play a crucial role in DNA repair. Mutations in other genes such as PTEN, TP53, and KRAS can also disrupt cell cycle regulation and promote uncontrolled proliferation. Individuals with a history of breast, endometrial, or colorectal cancer or endometriosis are at a higher risk. The most prevalent subtype is epithelial ovarian carcinoma, which typically arises from the surface epithelium of the ovary or the fallopian tube. Ovarian cancer progression involves multiple mechanisms, including suppression of apoptosis, activation of NF-κB and PI3K/AKT signaling, enhanced proliferation via EGFR/HER2 and MAPK/ERK pathways, metastasis mediated by EMT and MMPs, as well as metabolic and epigenetic alterations. Moreover, germline mutations linked to Lynch syndrome further increase the risk, and hereditary predisposition can be passed on depending on whether the mutated gene is dominant or recessive, with BRCA1/2 mutations being the most well-established.
Despite the considerable therapeutic potential of chemical and herbal anticancer agents, their clinical efficacy is often limited by poor solubility, high toxicity, and non-specific distribution, which reduce cellular uptake and overall treatment effectiveness. Recent studies have demonstrated that targeted drug delivery systems can overcome these barriers and significantly enhance therapeutic outcomes. The application of nanotechnology in cancer treatment, widely referred to as cancer nanotechnology, represents a promising approach. Nanoparticles, typically designed at the nanometer scale, are composed of diverse matrix materials and exhibit unique physicochemical properties such as surface charge, size, and morphology, making them highly suitable for biomedical and therapeutic applications. In drug delivery, nanoparticles generally range from 1 to 100 nanometers, but in some cases, their size can extend up to 1000 nanometers. Polymeric nanoparticles, consisting of drug molecules conjugated with polymers, are particularly useful for modifying drug release profiles and improving solubility. These systems act as efficient drug carriers, enabling targeted delivery to tumor cells while minimizing adverse effects on healthy tissues.Zein is a plant-derived protein extracted from corn that has recently gained significant attention as a natural biopolymer with high potential in the development of advanced drug delivery systems. Its unique features—including low immunogenicity, biodegradability, biocompatibility, resistance to harsh gastrointestinal conditions, and amphiphilic nature—make it a promising candidate for the design of sophisticated carriers. The characteristic brick-like structure of zein and its modifiable functional groups, such as hydroxyl and amine, allow extensive chemical functionalization. Due to its strong self-assembly capability and distinctive interfacial behavior, zein can form stable nanoparticles, nanofibers, nanomicelles, and nanogels.
Zein has proven particularly effective for encapsulating hydrophobic drugs such as curcumin, resveratrol, and quercetin, enhancing their stability during processing and storage. It is recognized as Generally Regarded as Safe (GRAS) by the FDA, confirming its reliability for pharmaceutical applications. Its high binding affinity toward hydrophobic molecules enables zein to retain drugs within its matrix, preventing premature leakage or degradation. Moreover, zein protects drugs against destructive environments such as gastric acid and digestive enzymes, while ensuring controlled release through gradual polymer degradation and diffusion, thereby maintaining effective drug concentrations for prolonged periods and improving bioavailability and therapeutic efficacy. Additionally, modified zein nanoparticles have been designed for controlled release of antibiotics in the gastrointestinal tract, successfully regulating drug release under simulated gut conditions and enhancing antibacterial activity.
Casein, a major milk protein, has also been explored as a versatile nanosystem for therapeutic and diagnostic applications. Sodium caseinate, the water-soluble derivative of casein, is widely applied as a stabilizer and emulsifier in the food and pharmaceutical industries. Compared to native casein, it exhibits improved solubility, which enhances its applicability in biomedical formulations. Its amphiphilic nature and ability to self-assemble into micellar structures make it an excellent carrier for both hydrophilic and hydrophobic drugs. Sodium caseinate can encapsulate bioactive compounds, protect them from enzymatic degradation, and modulate their release kinetics. Furthermore, it has been shown to improve the solubility and stability of poorly water-soluble drugs while providing sustained release, thereby prolonging circulation time and increasing therapeutic efficiency. Owing to their biocompatibility and safety, sodium caseinate-based nanocarriers represent a promising platform for the development of novel drug delivery systems.
Results: Ovarian cancer remains one of the most challenging malignancies due to late diagnosis, high recurrence rates, and the emergence of drug resistance. Conventional therapies, while widely applied, are often limited by poor efficacy and severe side effects. In this context, nanotechnology-based drug delivery systems have emerged as a promising approach to enhance therapeutic outcomes. Among various biopolymeric carriers, zein and sodium caseinate exhibit remarkable potential owing to their biocompatibility, biodegradability, and unique physicochemical properties. Zein, with its strong self-assembly capacity and high affinity for hydrophobic drugs, and sodium caseinate, with its superior solubility and micelle-forming ability, both offer efficient platforms for improving drug stability, solubility, and controlled release. Collectively, these natural protein-based nanocarriers provide new opportunities for the development of advanced and safer therapeutic strategies against ovarian cancer. Future studies should focus on clinical translation, large-scale production, and the optimization of multifunctional nanocarriers to fully exploit their potential in targeted and personalized cancer therapy
Conclusion: Ovarian cancer remains a life-threatening malignancy with limited treatment success due to late diagnosis, recurrence, and drug resistance. Nanotechnology offers a promising alternative to overcome these challenges by improving drug solubility, stability, and targeted delivery. Natural protein-based carriers such as zein and sodium caseinate demonstrate excellent biocompatibility, biodegradability, and the ability to provide controlled and sustained drug release. Their unique properties make them valuable platforms for developing safer and more effective therapeutic strategies. Continued research and clinical translation are essential to realize their full potential in ovarian cancer therapy