ABSTRACT
Localized heat generation from manganese iron oxide nanoparticles (MIONPs) conjugated with chemotherapeutics under the exposure of an alternating magnetic field (magneto-chemotherapy) can revolutionize targeted breast cancer therapy. On the other hand, the lack of precise control of local temperature and adequate MIONP distribution in laboratory settings using the conventional two-dimensional (2D) cellular models has limited its further translation in tumor sites. Our current study explored advanced 3D in vitro tumor models as a promising alternative to replicate the complete range of tumor characteristics. Specifically, we have focused on investigating the effectiveness of MIONP-based magneto-chemotherapy (MCT) as an anticancer treatment in a 3D breast cancer model. To achieve this, chitosan-coated MIONPs (CS-MIONPs) are synthesized and functionalized with an anticancer drug (doxorubicin) and a tumor-targeting aptamer (AS1411). CS-MIONPs with a crystallite size of 16.88 nm and a specific absorption rate (SAR) of 181.48 W g-1 are reported. In vitro assessment of MCF-7 breast cancer cell lines in 2D and 3D cell cultures demonstrated anticancer activity. In the 2D and 3D cancer models, the MIONP-mediated MCT reduced cancer cell viability to about 71.48% and 92.2%, respectively. On the other hand, MIONP-mediated MCT under an AC magnetic field diminished spheroids' viability to 83.76 ± 2%, being the most promising therapeutic modality against breast cancer.
ABSTRACT
Optimization of manganese-substituted iron oxide nanoferrites having the composition Mn x Fe1-x Fe2O4 (x = 0-1) has been achieved by the chemical co-precipitation method. The crystallite size and phase purity were analyzed from X-ray diffraction. With increases in Mn2+ concentration, the crystallite size varies from 5.78 to 9.94 nm. Transmission electron microscopy (TEM) analysis depicted particle sizes ranging from 10 ± 0.2 to 13 ± 0.2 nm with increasing Mn2+ substitution. The magnetization (M s) value varies significantly with increasing Mn2+ substitution. The variation in the magnetic properties may be attributed to the substitution of Fe2+ ions by Mn2+ ions inducing a change in the superexchange interaction between the A and B sublattices. The self-heating characteristics of Mn x Fe1-x Fe2O4 (x = 0-1) nanoparticles (NPs) in an AC magnetic field are evaluated by specific absorption rate (SAR) and intrinsic loss power, both of which are presented with varying NP composition, NP concentration, and field amplitudes. Mn0.75Fe0.25Fe2O4 exhibited superior induction heating properties in terms of a SAR of 153.76 W/g. This superior value of SAR with an optimized Mn2+ content is presented in correlation with the cation distribution of Mn2+ in the A or B position in the Fe3O4 structure and enhancement in magnetic saturation. These optimized Mn0.75Fe0.25Fe2O4 NPs can be used as a promising candidate for hyperthermia applications.
ABSTRACT
Cancer cell resistance to chemotherapeutics (chemoresistance) poses a significant clinical challenge that oncology research seeks to understand and overcome. Multiple anticancer drugs and targeting agents can be incorporated in nanomedicines, in addition to different treatment modalities, forming a single nanoplatform that can be used to address tumor chemoresistance. Nanomedicine-driven molecular assemblies using nucleic acids, small interfering (si)RNAs, miRNAs, and aptamers in combination with stimuli-responsive therapy improve the pharmacokinetic (PK) profile of the drugs and enhance their accumulation in tumors and, thus, therapeutic outcomes. In this review, we highlight nanomedicine-driven molecular targeting and therapy combination used to improve the 3Rs (right place, right time, and right dose) for chemoresistant tumor therapies.
