Biodegradable Polymeric Delivery Systems of Ruthenium(II) Polypyridyl Complexes for the Treatment of High-Grade Epithelial Ovarian Cancer

The design of effective nanotherapeutic platforms for cancer treatment remains a significant challenge in the field of medicinal inorganic chemistry. Herein, we report the development of Ru(II)-based nanotherapeutic systems specifically engineered for the treatment of high-grade epithelial ovarian cancer. By covalently conjugating a cytotoxic Ru(II) polypyridyl complex (Ru) to a biodegradable block copolymer composed of PEG and PLA, we achieved a high drug loading efficiency, improved aqueous solubility, and controlled drug release. The resulting nanoparticles exhibited optimal physicochemical properties, including uniform size distribution, excellent stability, and efficient cellular uptake, as confirmed by inductively coupled plasma mass spectrometry (ICP-MS). NP1 demonstrated enhanced tumor accumulation and a favorable biodistribution profile in vivo, confirming the effectiveness of the covalent encapsulation strategy using block copolymers. Although no significant tumor growth inhibition was observed in the challenging patient-derived xenograft (PDX) model OV54, the results provide valuable insights into the complex interplay between drug release kinetics, tumor biology, and therapeutic response.