pH-Thermo Dual-Responsive Polymeric Nanoparticles for Women’s Health: Dual Action Against Cervical and Ovarian Cancer Cells

The development of smart nanocarriers capable of responding to tumor-specific stimuli represents a promising strategy for improving therapeutic selectivity in oncology. In this work, we present a class of dual-responsive polymeric nanoparticles (NPs) engineered for precision drug delivery in gynecological cancers. Amphiphilic block copolymers of the type P(MAA)-<i>b</i>-P(EG₂MA-<i>co</i>-NIPAM) integrating pH-responsive methacrylic acid (MAA) and thermoresponsive diethylene glycol methyl ether methacrylate (EG₂MA) and <i>N</i>-isopropylacrylamide (NIPAM) units were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Fine-tuning of the lower critical solution temperature (LCST) was achieved by modulating the ratio between NIPAM and EG₂MA, yielding copolymers with cloud points within the physiologically relevant range of 30-40 °C. The resulting NPs exhibited sharp and reversible swelling/shrinking behavior in response to pH and temperature stimuli, with sizes below 182 nm and narrow polydispersity indexes. The core-shell architecture was stabilized by a dodecyl-functionalized chain transfer agent, ensuring efficient self-assembly and robust encapsulation of both hydrophilic and hydrophobic drugs. Drug release studies with 5-fluorouracil (5-FU) and the drug-mimetic fluorescein isothiocyanate (FITC) confirmed a marked temperature-triggered release above the LCST and enhanced diffusion in mildly acidic conditions (pH < 6), characteristic of solid tumors. Cellular studies on HeLa and ovarian adenocarcinoma OVCA433 lines revealed rapid internalization, high biocompatibility, and a significant increase in therapeutic efficacy of 5-FU when delivered via NPs, compared to the free drug. These findings highlight the potential of the dual-responsive nanoplatform for targeted and controlled delivery in the treatment of cervical and ovarian cancers.