Core–Shell UCNP@MOF Nanoplatforms for Dual Stimuli-Responsive Doxorubicin Release

Nanocarrier systems with multifunctional capabilities hold great potential for targeted cancer therapy, particularly for breast cancer treatment. Metal–organic frameworks (MOFs) are notable for their high porosity and, in some cases, biocompatibility, with ZIF-8 being particularly advantageous due to its pH-sensitive degradability, enabling selective drug release in tumor environments. Additionally, lanthanide-doped upconversion nanoparticles (UCNPs) offer unique optical properties that enhance both imaging and therapeutic applications. In this study, NaYF₄/Yb³⁺Er³⁺ UCNPs were synthesized via a hydrothermal method, subsequently coated with poly(acrylic acid) (PAA) and encapsulated within a ZIF-8 shell, forming of UCNP@ZIF-8 core–shell nanocomposites. This system was designed to leverage stimulation by a 980 nm laser and acidic pH to facilitate drug release. When exposed to this specific laser wavelength, the nanocomposites demonstrated significantly enhanced drug release, achieving up to 90% release of the incorporated antitumor drug, doxorubicin (DOX), in acidic environments. In vitro studies indicated selective cytotoxicity, with MCF-7 tumor cell viability decreasing from 85.7% to 20% following laser activation, while showing minimal toxicity toward healthy cells. These findings underscore the potential of the UCNP@ZIF-8 nanocarrier system as a pH and laser-responsive platform for improved cancer therapy, enabling precise control over drug delivery while minimizing side effects on surrounding healthy tissues.