Preliminary study on targeted nanoparticles co-loaded with piperine and paclitaxel prodrug for ovarian cancer treatment

Abstract

Combination chemotherapy incorporating natural products has emerged as an effective strategy to enhance anticancer efficacy while reducing systemic toxicity. Based on this, our study report a targeted, stimuli-responsive nanoparticle system for the co-delivery of paclitaxel (PTX) and piperine (PIP) to achieve synergistic ovarian cancer therapy. PTX was chemically conjugated to polyamidoamine (PAMAM) dendrimers via a glutathione (GSH)-sensitive disulfide linkage, while PIP was physically encapsulated within the hydrophobic core of PAMAM. Hyaluronic acid (HA) was subsequently electrostatically assembled onto the nanoparticle surface to enable CD44-mediated tumor targeting. The resulting nanoparticles exhibited a uniform spherical morphology with an average diameter of approximately 145 nm and demonstrated dual responsiveness to elevated GSH and acidic pH conditions characteristic of the tumor microenvironments. In vitro and in vivo antitumor studies revealed that the co-delivery system significantly enhanced cytotoxicity and apoptosis through synergistic PTX/PIP activity compared with monotherapy. In addition, HA modification markedly improved cellular uptake and tumor accumulation, leading to effective tumor growth inhibition in vivo with reduced systemic toxicity. In conclusion, this study highlights a rationally engineered nanocarrier integrating active targeting and stimuli-responsive release, offering a promising materials-based strategy for synergistic ovarian cancer therapy.