Multi-stimuli-responsive chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles as theranostic platforms for combined tumor magnetic resonance imaging and chemotherapy

• Published in: Nanomedicine 2023-08, Vol.52, p.102695-102695, Article 102695
• Main Authors: García-García, Gracia, Caro, Carlos, Fernández-Álvarez, Fátima, García-Martín, María Luisa, Arias, José L.
• Format: Article
• Language: English
• Subjects: Chitosan; Dual pH- and heat-triggered drug release; Magnetic resonance imaging; Magnetite; Poly(ε-caprolactone)
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2023.102695

Chitosan-functionalized magnetite/poly(ε-caprolactone) nanoparticles were formulated by interfacial polymer disposition plus coacervation, and loaded with gemcitabine. That (core/shell)/shell nanostructure was confirmed by electron microscopy, elemental analysis, electrophoretic, and Fourier transform infrared characterizations. A short-term stability study proved the protection against particle aggregation provided by the chitosan shell. Superparamagnetic properties of the nanoparticles were characterized in vitro, while the definition of the longitudinal and transverse relaxivities was an initial indication of their capacity as T2 contrast agents. Safety of the particles was demonstrated in vitro on HFF-1 human fibroblasts, and ex vivo on SCID mice. The nanoparticles demonstrated in vitro pH- and heat-responsive gemcitabine release capabilities. In vivo magnetic resonance imaging studies and Prussian blue visualization of iron deposits in tissue samples defined the improvement in nanoparticle targeting into the tumor when using a magnetic field. This tri-stimuli (magnetite/poly(ε-caprolactone))/chitosan nanostructure could find theranostic applications (biomedical imaging & chemotherapy) against tumors. Reproducible formulation of chitosan-functionalized magnetite/poly(ε-caprolactone) particles that may constitute a potential theranostic nanotool (biomedical imaging & chemotherapy) against cancer. This multifunctional (core/shell)/shell nanostructure exhibited a tri-stimuli responsive behavior: magnetism, and pH- and heat-triggered drug release. In vitro and in vivo proof of concepts highlighted their use as T2 contrast agents, and the significant improvement of nanoparticle delivery to the tumor site by an applied magnetic field. [Display omitted] •(Core/shell)/shell NPs with potential theranostic applications against cancer•Tri-stimuli responsive behavior: magnetism, and pH- and heat-triggered drug release•In vitro and in vivo proof of concepts of their use as T2 contrast agents•NP delivery to the tumor site significantly improved by an external magnetic field