Polybasic nanogels for intracellular co-delivery of paclitaxel and carboplatin: a novel approach to ovarian cancer therapy

Abstract

Ovarian cancer is one of the leading causes of cancer-related deaths in women, with limited progress in treatments despite decades of research. Common treatment protocols rely on surgical removal of tumors and chemotherapy drugs, such as paclitaxel and carboplatin, which are capable of reaching cancer cells throughout the body. However, the effectiveness of these drugs is often limited due to toxic reactions in patients, nonspecific drug distribution affecting healthy cells, and the development of treatment resistance. In this study, we introduce a polybasic nanogel system composed of poly(diethylaminoethyl methacrylate-co-cyclohexyl methacrylate)-g-poly(ethylene glycol) designed for the targeted co-delivery of paclitaxel and carboplatin directly to ovarian cancer cells. These nanogel systems can respond to the cellular microenvironment to achieve controlled, on-demand drug release, reducing off-target effects and enhancing therapeutic uptake. Additionally, we investigated nanoparticle degradation and controlled drug release as a function of various crosslinkers, including tetraethylene glycol dimethacrylate, bis(2-methacryloyl)oxyethyl disulfide, poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid)dimethacrylate, and polycaprolactone dimethacrylate. Our results, using OVCAR-3 human ovarian cancer cells, demonstrated that this dual-delivery system outperformed free drugs in inducing cancer cell death, representing a promising advance in the field of nanoparticle-based therapies for ovarian cancer. By loading two chemotherapeutic agents into a single, environmentally responsive particle, this approach shows the potential to overcome common resistance mechanisms and achieve more effective tumor suppression. In summary, by delivering chemotherapy more precisely, it may be possible to enhance therapeutic outcomes while minimizing toxicity and nonspecific drug distribution, ultimately improving patient quality of life.