A Multifunctional, Highly Biocompatible, and Double-Triggering Caramelized Nanotheranostic System Loaded with Fe3O4 and DOX for Combined Chemo-Photothermal Therapy and Real-Time Magnetic Resonance Imaging Monitoring of Triple Negative Breast Cancer

Abstract

Purpose: Owing to lack of specific molecular targets, the current clinical therapeutic strategy for triple negative breast cancer (TNBC) is still limited. In recent years, some nanosystems for malignancy treatment have received considerable attention. In this study, we prepared caramelized nanospheres (CNSs) loaded with doxorubicin (DOX) and Fe₃O₄ to achieve the synergistic effect of combined therapy and real-time magnetic resonance imaging (MRI) monitoring, so as to improve the diagnosis and therapeutic effect of TNBC.

Methods: CNSs with biocompatibility and unique optical properties were prepared by hydrothermal method, DOX and Fe₃O₄ were loaded on it to obtain Fe₃O₄/DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe₃O₄/DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe₃O₄@CNSs, DOX and Fe₃O₄/DOX@CNSs were examined in vitro or in vivo.

Results: Fe₃O₄/DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe₃O₄/DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe₃O₄/DOX@CNSs proved that it can be used in vivo. Fe₃O₄/DOX@CNSs displayed high photothermal conversion efficiency, extensive pH/heat-induced DOX release. 70.3% DOX release is observed under the 808 nm laser in the pH = 5 PBS solution, obviously higher than pH = 5 (50.9%) and pH = 7.4 (less than 10%). Pharmacokinetic experiments indicated the t1/2β, and AUC_0-t of Fe₃O₄/DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe₃O₄/DOX@CNSs with NIR had the greatest tumor suppression in vitro and in vivo. Moreover, this nanosystem demonstrated distinct contrast enhancement on T2 MRI to achieve real-time imaging monitoring during treatment.

Conclusion: Fe₃O₄/DOX@CNSs is a highly biocompatible, double-triggering and improved DOX bioavailability nanosystem that combines chemo-PTT and real-time MRI monitoring to achieve integration of diagnosis and treatment of TNBC.

Keywords: caramelized nanotheranostic system; combining chemo-photothermal therapy; double-triggering; magnetic resonance imaging monitoring; triple negative breast cancer.