Facile preparation of a pH-sensitive biocompatible nanocarrier based on magnetic layered double hydroxides/Cu MOFs-chitosan crosslinked к-carrageenan for controlled doxorubicin delivery to breast cancer cells

Abstract

Recently, the biocompatibility of hydrogel nanoparticles has gained considerable research attention in the field of drug delivery. In this regard, we design a pH-controlled nanocarrier based on magnetic layered double hydroxides/copper metal-organic framework-chitosan crosslinked к-carrageenan hydrogel nanoparticles (LDH-Fe₃O₄/Cu MOF-DOX-CS@CAR) for targeted release from DOX to breast cancer cells. FT-IR, EDX, XRD, FE-SEM, VSM, and Zeta potential investigated the chemical structure of hydrogel nanoparticles. The encapsulation efficiency and drug loading capacity of the DOX were obtained to be 96.1 % and 9.6 %, respectively. The cumulative release of DOX from LDH-Fe₃O₄/Cu MOF-DOX-CS@CAR at pH 5.5 and 7.4 after 72 h was 60.3 % and 22.6 %, respectively. These in vitro release results confirmed the controlled release and pH-response behavior of hydrogel nanoparticles. Also, the mechanism of DOX release from LDH-Fe₃O₄/Cu MOF-DOX-CS@CAR hydrogel nanoparticles showed that the Korsmeyer-Peppas model with Fickian diffusion is the best-fitting model for describing the release behavior of DOX from hydrogel nanoparticles. The cellular cytotoxicity and DAPI tests of the prepared LDH and LDH-Fe₃O₄/Cu MOF toward L929 non-cancerous cells and MCF-7 breast cancer cells confirm its relative biocompatibility and safety. Whereas, LDH-Fe₃O₄/Cu MOF-DOX-CS@CAR hydrogel nanoparticles toward MCF-7 breast cancer cells had higher cytotoxicity effects due to the targeted and controlled release of DOX to MCF-7 cells. The in vitro DPPH, hemolysis assay, colloidal stability, and enzymatic degradation proved the excellent antioxidant activity (71.81 %), blood compatibility (less than 5 %), better stability, and biodegradation behavior of hydrogel nanoparticles. On these findings, the present study suggests the potential of the prepared LDH-Fe₃O₄/Cu MOF-DOX-CS@CAR hydrogel nanoparticles as a pH-controlled drug delivery system for cancer treatment and various biomedical uses.

Keywords: Chitosan@к-carrageenan; Hydrogel nanoparticles; Layered double hydroxide; Metal-organic framework; pH-Controlled system.