Mineral Nanomedicine to Enhance the Efficacy of Adjuvant Radiotherapy for Treating Osteosarcoma

Abstract

It is vital to remove residual tumor cells after resection to avoid the recurrence and metastasis of osteosarcoma. In this study, a mineral nanomedicine, europium-doped calcium fluoride (CaF 2 :Eu) nanoparticles (NPs), is developed to enhance the efficacy of adjuvant radiotherapy (i.e., surgical resection followed by radiotherapy) for tumor cell growth and metastasis of osteosarcoma. In vitro studies show that CaF 2 :Eu NPs (200 μg/ mL) exert osteosarcoma cell (143B)-selective toxicity and migration-inhibiting effects at a Eu dopant amount of 2.95 atomic weight percentage. These effects are further enhanced under X-ray irradiation (6 MeV, 4 Gy). Furthermore, in vivo tests show that intraosseous injection of CaF 2 :Eu NPs and X-ray irradiation have satisfactory therapeutic efficacy in controlling primary tumor size and inhibiting primary tumor metastasis. Overall, our results suggest that CaF 2 :Eu NPs with their osteosarcoma cell (143B)-selective toxicity and migrationinhibiting effects combined with radiotherapy might be nanomedicines for treating osteosarcoma after tumor resection.

Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy

“…Wang et al first found that CaF 2 NPs may be selectively toxic to tumor cells. They developed a europium (Eu)-doped CaF 2 NPs to inhibit the growth and migration of osteosarcoma [ 98 ]. Moreover, CaF 2 material can increase cell adhesion and inhibit tumor metastasis and cooperate with Eu to inhibit the recurrence and metastasis of residual tumor cells.…”

Immunogenic Radiation Therapy for Enhanced Antitumor Immunity via a Core–Shell Nanosensitizer-Mediated Immunosuppressive Tumor Microenvironment Modulation

“…The percentage of 4T1 cells at the G2/M phase was higher for UM (15.0%) than that in the PBS group (6.6%, Figure B). Compared with other phases, cells in the G2/M phase have the highest sensitivity in response to radiation. − We hypothesized that more UM pretreated cells would die under X-ray irradiation. As shown in Figure A,C, at a given concentration of 100 μg/mL and subsequent X-ray irradiation at 4 Gy, the 4T1 cell viability decreased dramatically from 91.0% for UiO to 15.7% for UM, which was even 20.7% lower than the predicted cell viability, certifying that the response of 4T1 cells to X-ray was boosted upon UM pretreatment.…”

Manipulating calcium homeostasis with nanoplatforms for enhanced cancer therapy

“…CaP TiO 2 @CaP Ca 2+ overload, SDT [155] lipid-CaP-Cu 2+ -disulfiram (DSF)(Cu-LCP/DSF NPs) CaP as nanocarrier, ICD [62] CaBPs Ca 2+ overload, changing the osmotic pressure [156] Fe/Se-CaP Boost adaptive immune response [113] CM@CaP NGs Increase the delivery and uptake efficiency of antigens, induce immune responses [27] OMV@CaP Neutralize tumour acidity, M2-to-M1 polarization [123] CaS ZnPP@PAA-CaS Ca 2+ overload, tumour calcification, induce ICD [71] CaF 2 CaF 2 Ca 2+ overload, peroxidase (POD)-mimicking activity by generating ROS [76] CaF 2 :Eu NPs Carrier, scintillator, Ca 2+ -induced radiosensitization [157] Compared to traditional therapies that use drugs to control Ca 2+ levels, these burgeoning nanoplatform-based strategies for regulating Ca 2+ homeostasis have several advantages. Firstly, nanomaterials can be precisely targeted to reduce the adverse effects of Ca 2+ on normal cells and tissues.…”