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

TL;DR

This paper introduces smart nanoparticles that respond to pH and temperature to deliver drugs more effectively to cervical and ovarian cancer cells.

Contribution

The novelty lies in the dual-responsive polymeric nanoparticles combining pH and thermal sensitivity for targeted drug delivery in gynecological cancers.

Findings

Nanoparticles showed sharp and reversible swelling/shrinking behavior in response to pH and temperature changes.

Drug release was significantly enhanced under tumor-like acidic conditions and above the lower critical solution temperature.

5-fluorouracil delivered via nanoparticles showed increased therapeutic efficacy in cervical and ovarian cancer cells.

Abstract

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)-b-P­(EG2MA-co-NIPAM) integrating pH-responsive methacrylic acid (MAA) and thermoresponsive
diethylene glycol methyl ether methacrylate (EG2MA) and N-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.

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