This work presents the development of a facile ligand-assisted hydrothermal reaction for the preparation of NIR-activated Fe(3)O(4) nanostructures that can directly upgrade the iron oxide with MR contrast ability to be a MRI/photothermal theranostic agent.
Cu@CuO@PSMA polymer nanoparticles (Cu@CuO@polymer NPs) with near-infrared (NIR) absorption were successfully synthesized in a single-step oxidation reaction of Cu@PSMA polymer NPs at 100 °C for 20 min. The shape, structure, and optical properties of the Cu@CuO@polymer NPs were tailorable by controlling the reaction parameters, for example, using the initial Cu@PSMA polymer NP as a template and varying the halide ion content, heating temperature, and reaction time. The Cu@CuO@polymer NPs exhibited robust NIR absorption between 650 and 710 nm and possessed superior oxidation resistance in water and culture media. In vitro assays demonstrated the low cytotoxicity of the Cu@CuO@PSMA polymer NPs to HeLa cells through an improved cell viability, high IC, low injury incidence from the supernatant of the partly dissociated Cu@CuO@PSMA polymer NPs, and minor generation of reactive oxygen species. More importantly, we demonstrated that the inorganic Cu-based nanocomposite [+0.34 V vs normal hydrogen electrode (NHE)] was degradable in an endogenous HO (+1.78 V vs NHE) environment. Cu ions were detected in the urine of mice, which illustrates the possibility of extraction after the degradation of the Cu-based particles. 'After an treatment of the HeLa cells with the Cu@CuO@polymer NPs and a 660 nm light-emitting diode, the photoablation of 50 and 90% cells was observed at NP doses of 20 and 50 ppm, respectively. These results demonstrate that NIR-functional and moderate redox-active Cu@CuO@polymer NPs are potential next-generation photothermal therapy (PTT) nanoagents because of combined features of degradation resistance in the physiological environment, enabling the delivery of efficient PTT, a possibly improved ability to selectively harm cancer cells by releasing Cu ions under high-HO and/or low-pH conditions, and ability to be extracted from the body after biodegradation.
We developed a simple emulsion and solvent-evaporation approach for the clustering of iron oxide nanoparticles using a polyethylene glycol (PEG)-based nonionic surfactant, D-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS). To obtain well-constructed clusters of iron oxide nanoparticles (IONPs), the synthetic parameters (the solvent systems and reaction temperature) were investigated. The rate of solvent evaporation is critical to optimise the formation of clusters which were spherical in shape, had a diameter of approximately 97 nm, and were highly stable for storage at room temperature. This greener synthetic approach displays the benefits of high yield and waste reduction compared to previous reports. In addition, IONP clusters of 50 mg mL 1 retained over 84% of the viability of KB cells and the structure of the clusters can be observed by transmission electron microscopy after cellular internalisation. The mechanism of cellular uptake of the IONP clusters was speculated to be via an energy-dependent endocytic pathway because the internalisation was significantly inhibited at 4 C. These IONP clusters also had higher saturation magnetisation and r2 relaxation (253.85 s 1 mM 1) values and better T2-weighted contrast performance (r2/r1 � 20.5) than commercial Resovist . The contrast signal for magnetic resonance imaging was efficiently increased by the IONP clusters in vivo, especially in the liver and tumour regions. Iron staining of both tissues confirmed the accumulation of the nanoparticles in both areas. Thus, these clusters, which were prepared with the use of a nonionic polymer surfactant, can potentially serve as efficient contrast agents for magnetic resonance applications
Cancer has become one of the major diseases of human health around the world. Conventional antitumor drugs cannot specifically target cancers and result in serious side effects. To achieve better therapy, innovative functional drug delivery platforms that will aid specific targeting for cancer cells need to be developed. In this study, transferrin (Tf), which can target cancer cells, is covalently anchored onto the surface of MSNPs via disulfide linkage, which is used for glutathione-triggered intracellular drug release in tumor cells. The successful functionalization of redox-responsive MSNPs is confirmed by using BET/BJH, TEM, TGA, NMR, and FT-IR (BET, Brunauer–Emmett–Teller; BJH, Barrett–Joyner–Halenda). In addition, polyethylene glycol (PEG) is further grafted onto the surface of MSNPs to improve the biocompatibility and stability under physiological conditions for longer blood circulation. Our in vitro studies demonstrate that DOX-loaded MSNP–SS–Tf@PEG can selectively be internalized into cancer cells via Tf/Tf receptor interactions, and then, DOX is released in HT-29 and MCF-7 cells triggered by high GSH concentration in tumor cells. Remarkably, in vivo studies demonstrate that DOX-loaded MSNP–SS–Tf@PEG can significantly inhibit tumor growth with minimized side effects through cell apoptosis determined by TUNEL assay, whereas MSNP–SS–Tf@PEG revealed no significant inhibition. In conclusion, DOX–MSNP–SS–Tf@PEG with active targeting moieties and a redox-responsive strategy has been demonstrated as a great effective drug carrier for tumor therapy in vitro and in vivo.
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