Carboxymethyl chitosan-modified pH/redox dual-responsive hollow mesoporous manganese dioxide nanoparticles for targeted delivery of emodin in breast cancer.

Emodin is a natural anthraquinone derivative with a variety of pharmacological effects such as anti-inflammatory and anti-cancer. However, its clinical application is hindered by poor water solubility and low bioavailability. To address these limitations, we developed carboxymethyl chitosan and poly(acrylic acid)/poly(allylamine hydrochloride)-modified hollow mesoporous manganese dioxide nanoparticles (CPPMNP) for emodin loading (ECPPMNP). The zeta potential of ECPPMNP was -26.4 ± 0.5 mV, the average particle size was (67.2 ± 4.7) nm, and the drug loading and encapsulation efficiency were (23.90 ± 0.29) % and (62.80 ± 0.99) %, respectively. In vitro studies, cell experiments confirmed that ECPPMNP were efficiently internalized by MDA-MB-231 triple-negative breast cancer cells, facilitating emodin release and significantly suppressing intracellular reactive oxygen species production, thereby inhibiting tumor cell proliferation. Due to the introduction of amide bonds on the surface of the nanoparticles, the nanoparticles have pH/redox dual-responsiveness, which allows them to effectively achieve controlled release of emodin at tumor sites that are more acidic and abundantly expressed glutathione. In vivo anti-tumor experiments showed that ECPPMNP significantly aggregated at the tumor site and inhibited the growth of subcutaneous tumors in nude mice, and the final tumor inhibition rate reached 81.9%. This nanocarrier system has good biocompatibility and is expected to be an effective therapeutic strategy in the field of triple negative breast cancer treatment in the future.