Superparamagnetic Iron Oxide-Erastin-Polyethylene Glycol Nanotherapeutic Platform: A Ferroptosis-Based Approach for the Integrated Diagnosis and Treatment of Nasopharyngeal Cancer.

Erastin can induce ferroptosis in tumor cells as an effective small molecule inhibitor. However, its application is hampered by a lack of water solubility. This study investigated the effects of superparamagnetic iron oxide (SPIO)-erastin-polyethylene glycol (PEG) nanoparticles prepared by loading SPIO-PEG nanoparticles with erastin on ferroptosis. SPIO-erastin-PEG nanoparticles exhibited square and spherical shapes with good dispersibility. The zeta potential and hydrodynamic size of SPIO-erastin-PEG were measured as (-37.68 ± 2.706) mV and (45.75 ± 18.88) nm, respectively. On T2-weighted imaging, the nanosystem showed significant contrast enhancement compared to no-enhancement magnetic resonance imaging (MRI). SPIO-erastin-PEG induced ferroptosis by increasing reactive oxygen species and iron content and promoting the accumulation of lipid peroxides and the degradation of glutathione peroxidase 4. Pharmacokinetic experiments revealed a half-life of 1.25 ± 0.05 h for the SPIO-erastin-PEG solution in circulation. Moreover, significant antitumorigenic effects of SPIO-erastin-PEG have been demonstrated in 5-8F cells and mouse-bearing tumors. These results indicated that the synthesized SPIO-erastin-PEG nanoplatform could induce ferroptosis effects in vitro and in vivo while exhibiting favorable physical characteristics. This approach may provide a new strategy for theranostic nanoplatform for nasopharyngeal cancer.

Polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X nanotheranostic platform for nasopharyngeal carcinoma imaging and photothermal therapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of head and neck malignant tumor with a high incidence in specific regional distribution, and its traditional therapies face some challenges. It has become an urgent need to seek new therapeutic strategies without or with low toxicity and side effects. At present, more and more researchers has been attracting attention by nanotheranostic platform. Therefore, our team synthesized the polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X (USPIO-PEG-sLex) nanotheranostic platform with high temperature pyrolysis. RESULTS: The USPIO-PEG-sLex nanoparticles had excellent photothermal conversion property, and the temperature of USPIO-PEG-sLex nanoparticles solution increased with its concentration and power density of near-infrared (NIR) on 808 nm wavelengths. Five USPIO-PEG-sLex nanoparticles with different concentrations of 0 mg/ml, 0.025 mg/ml, 0.05 mg/ml, 0.1 mg/ml and 0.2 mg/ml were prepared. The biological toxicity results showed that the viability of NPC 5-8F cells is related to the concentration of USPIO-PEG-sLex nanoparticles and the culture time (P < 0.001). The results of photothermal therapy (PTT) in vitro indicated that the viability of 5-8F cells decreased significantly with the concentration of USPIO-PEG-sLex nanoparticles increases (P < 0.001), and the viability of NPC 5-8F cells were 91.04% ± 5.20%, 77.83% ± 3.01%, 73.48% ± 5.55%, 59.50% ± 10.98%, 17.11% ± 3.14%, respectively. The USPIO-PEG-sLex nanoparticles could target the tumor area, and reduce the T2* value of tumor tissue. The T2* values of tumor pre- and post-injection were 30.870 ± 5.604 and 18.335 ± 4.351, respectively (P < 0.001). In addition, USPIO-PEG-sLex nanoparticles as a photothermal agent for PTT could effectively inhibit tumor progression. The ratio of volume change between tail vein injection group, control group, nanoparticles without laser irradiation group and blank group after 5 treatments were 3.04 ± 0.57, 5.80 ± 1.06, 8.09 ± 1.96, 7.89 ± 2.20, respectively (P < 0.001). CONCLUSIONS: Our synthesized USPIO-PEG-sLex nanotheranostic platform, and it may be become a new strategy for the treatment of NPC.

Ultrasmall superparamagnetic nanoparticles targeting E-selectin: synthesis and effects in mice in vitro and in vivo.

Purpose: We developed a contrast agent for targeting E-selectin expression. We detected the agent using magnetic resonance imaging (MRI) in vivo in nude mice that had undergone nasopharyngeal carcinoma (NPC) metastasis. Methods: Sialyl Lewis X (sLeX) was conjugated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Hydrodynamic size, polydispersity index, and ζ-potential of USPIO-polyethylene glycol (PEG) nanoparticles and USPIO-PEG-sLeX nanoparticles were measured. Component changes in nanoparticles of USPIO, USPIO-PEG, and USPIO-PEG-sLeX were analyzed by thermogravimetric analysis and Fourier-transform infrared spectroscopy. A model of NPC metastasis to inguinal lymph nodes in nude mice was used to investigate characteristics of the USPIO-PEG-sLeX nanoparticles in vivo. We investigated the ability of the T2* value, change in T2* value (ΔT2* value), and enhancement rate (ER) to assess accumulation of USPIO-PEG-sLeX nanoparticles quantitatively in mice of a metastasis group and control group. Four MRI scans were undertaken for each mouse. The first scan (t0) was done before administration of USPIO-PEG-sLeX nanoparticles (0.1 mL) via the tail vein. The other scans were carried out at 0 (t1), 1 (t2), and 2 hours (t3) postinjection. The mean optical density was used to reflect E-selectin expression. Results: sLeX was labeled onto USPIO successfully. In vivo, there were significant interactions between the groups and time for T2* values after administration of USPIO-PEG-sLeX nanoparticles. Six parameters (T2* at t2, ΔT2* at t1, ΔT2* at t2, ER at t1, ER at t2, and ER at t3) were correlated with the mean optical density. Conclusion: USPIO-PEG-sLeX nanoparticles can be used to assess E-selectin expression quantitatively. Use of such molecular probes could enable detection of early metastasis of NPC, more accurate staging, and treatment monitoring.