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 Fe 3 O 4 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 Fe 3 O 4 were loaded on it to obtain Fe 3 O 4 /DOX@CNSs nanosystem. Characteristics including morphology, hydrodynamic size, zeta potentials and magnetic properties of Fe 3 O 4 /DOX@CNSs were evaluated. The DOX release was evaluated by different pH/near-infrared (NIR) light energy. Biosafety, pharmacokinetics, MRI and therapeutic treatment of Fe 3 O 4 @CNSs, DOX and Fe 3 O 4 /DOX@CNSs were examined in vitro or in vivo. Results Fe 3 O 4 /DOX@CNSs has an average particle size of 160 nm and a zeta potential of 27.5mV, it demonstrated that Fe 3 O 4 /DOX@CNSs is a stable and homogeneous dispersed system. The hemolysis experiment of Fe 3 O 4 /DOX@CNSs proved that it can be used in vivo. Fe 3 O 4 /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 Fe 3 O 4 /DOX@CNSs were 1.96 and 1.31 -fold higher than those of DOX solution, respectively. Additionally, Fe 3 O 4 /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 Fe 3 O 4 /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.

Fe3O4-Cy5.5-trastuzumab magnetic nanoparticles for magnetic resonance/near-infrared imaging targeting HER2 in breast cancer

“…In terms of magnetic resonance properties, Fe 3 O 4 -Cy5.5-trastuzumab had a magnetization saturation intensity of 27.58 emg g −1 with negligible coercivity, but its T 2 relaxation rate still reached 42.29 mM −1 s −1 , and it also exhibited a clear trend of weakened imaging signals in vitro T 2 imaging, which indicated that nanoparticles connecting the monoclonal antibody and the fluorescent molecule did not significantly affect its performance in T 2 imaging [46,47]. In addition, combined with in vivo magnetic resonance imaging, Fe 3 O 4 -Cy5.5-trastuzumab nanoparticles showed a good targeting performance in magnetic resonance imaging [48][49][50][51].…”

Combination of Chlorambucil and Mercaptopurine Show Effective Anti-Cancer Effects in Mice Model

“…Hemolysis rates falling within the ranges of 0–2%, 2–5%, and 5–100% were categorized as non-hemolytic, mildly hemolytic, and hemolytic, respectively. 32 , 33 In this work, the hemolysis tests of the poly(HPMA)-Chl-PTA conjugate were processed and summarized in Figure S5 . PBS and pure water served as the positive and negative controls, which resulted in no hemolysis and significant hemolysis, respectively.…”