Enhancing breast cancer therapy: optimizing drug delivery using ruthenium polypyridyl II and Olaparib both individually and co-loaded with ZIF-8 nanoparticles

Abstract

Combinational therapy has become a widely adopted strategy in cancer treatment, offering benefits such as reduced dosages, decreased toxicity, and prevention of drug resistance. A ruthenium polypyridyl complex (RuPIP) has emerged as a promising alternative to platinum-based drugs, particularly effective when combined with poly(ADP-ribose) polymerase (PARP) inhibitors (Olaparib). This study synthesized a biocompatible zeolitic imidazolate framework-8 (ZIF-8) for encapsulating and co-loading both drugs. High encapsulation ratios were achieved within the ZIF-8 framework in just 25 minutes, yielding encapsulation efficiencies of 90.18% for RuPIP and 89.49% for Olap. The physicochemical characteristics and release profiles of both drugs were thoroughly evaluated. Drug release was monitored under acidic pH conditions, simulating tumor microenvironments, and compared to release at a physiological pH of 7.3. Characterization was performed using X-ray diffraction, field emission scanning electron microscopy (FESEM), Brunauer–Emmett–Teller (BET) surface area analysis, and high-performance liquid chromatography (HPLC). Additionally, in vitro cytotoxic effects were investigated against three cell lines: HaCaT (normal cells), MCF-7, and MDA-MB-231 breast cancer cells. Results indicated that the combination of both drugs exhibited significant cytotoxicity in MCF 7 and MDA-MB-231 cells, with minimal effects on HaCaT cells. The pH-responsive RuPIP–Olap@ZIF-8 shows considerable potential for targeted breast cancer therapy, paving the way for future clinical trials.