The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) (<5 nm) are promising T-weighted contrast agents for magnetic resonance imaging (MRI) due to their good biocompatibility compared with Gd-chelates. However, the best particle size of ES-MIONs for T imaging is still unknown because the synthesis of ES-MIONs with precise size control to clarify the relationship between the r (or r/r) and the particle size remains a challenge. In this study, we synthesized ES-MIONs with seven different sizes below 5 nm and found that 3.6 nm is the best particle size for ES-MIONs to be utilized as T-weighted MR contrast agent. To enhance tumor targetability of theranostic nanoparticles and reduce the nonspecific uptake of nanoparticles by normal healthy cells, we constructed a drug delivery system based on the 3.6 nm ES-MIONs for T-weighted tumor imaging and chemotherapy. The laser scanning confocal microscopy (LSCM) and flow cytometry analysis results demonstrate that our strategy of precise targeting via exposure or hiding of the targeting ligand RGD on demand is feasible. The MR imaging and chemotherapy results on the cancer cells and tumor-bearing mice reinforce that our DOX@ES-MION3@RGD@mPEG3 nanoparticles are promising for high-resolution T-weighted MR imaging and precise chemotherapy of tumors.

White TiO2 nanoparticles (NPs) have been widely used for cancer photodynamic therapy based on their ultraviolet light-triggered properties. To date, biomedical applications using white TiO2 NPs have been limited, since ultraviolet light is a well-known mutagen and shallow penetration. This work is the first report about hydrogenated black TiO2 (H-TiO2 ) NPs with near infrared absorption explored as photothermal agent for cancer photothermal therapy to circumvent the obstacle of ultraviolet light excitation. Here, it is shown that photothermal effect of H-TiO2 NPs can be attributed to their dramatically enhanced nonradiative recombination. After polyethylene glycol (PEG) coating, H-TiO2 -PEG NPs exhibit high photothermal conversion efficiency of 40.8%, and stable size distribution in serum solution. The toxicity and cancer therapy effect of H-TiO2 -PEG NPs are relative systemically evaluated in vitro and in vivo. The findings herein demonstrate that infrared-irradiated H-TiO2 -PEG NPs exhibit low toxicity, high efficiency as a photothermal agent for cancer therapy, and are promising for further biomedical applications.

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Multifunctional Fe(3)O(4)-TiO(2) nanocomposites with Janus structure for magnetic resonance imaging (MRI) and potential photodynamic therapy (PDT) were synthesized, in which Fe(3)O(4) was used as a MRI contrast agent and TiO(2) as an inorganic photosensitizer for PDT. Their morphology, structure, and MRI and PDT performance were characterized, respectively. Moreover, the location of Fe(3)O(4)-TiO(2) nanocomposites in MCF-7 cells was also investigated by the staining of Prussian blue and alizarin red, respectively. The results showed that the as-prepared Fe(3)O(4)-TiO(2) nanocomposites had good T(2)-weighted MRI performance, and the MCF-7 cells incubated with nanocomposites could be killed under the irradiation of UV light. Compared with traditional organic photosensitizers, TiO(2) inorganic photosensitizers could have more stable PDT performance due to their nanoscale size and anti-photodegradable stability. Therefore, the as-prepared Fe(3)O(4)-TiO(2) nanocomposites could have potential applications as a new kind of multifunctional agent for both MRI and PDT.

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Magnetic resonance imaging (MRI), a sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has intrinsic advantage in safety compared with radiotracer and optical imaging modalities. However, MRI contrast agents are less sensitive than complexes used in other imaging techniques. Usually clinical used Gd-based complexes MRI-T 1 contrast agents are toxic. Therefore, demand for nontoxic novel T 1 -weighted MRI potential candidate with ultrasensitive imaging and advanced functionality is very high. In this research, silica coated ultra small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via thermal decomposition method which demonstrated high performance T 1 -weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses.Transmission electron microscopy (TEM) results have illustrated that the diameter of SPIONPs was in the range of 4nm and the average size of Fe 3 O 4 @SiO 2 was about 30~40nm. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the purity in phase of the prepared SPIONPs. These magnetite nanoparticles exhibited weak magnetic moment at room temperature because of spin-canting effect which escorted high positive signal enhancement ability. MTT assays and histological analysis demonstrated good biocompatibility of the SPIONPs in vitro and in vivo. In addition, the silica coated ultra small (4nm-sized) magnetite nanoparticles exhibited a good r 1 relaxivity of 1.2mM -1 s -1 and low r 2 /r 1 ratio of 6.5 mM -1 s -1 . In vivo T 1 -weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of as-synthesized magnetite nanoparticles. These results reveal silica coated SPIONPs as a promising candidate for T 1 contrast agent with extraordinary capability to enhance MR images.

Nanotechnology has introduced new techniques and phototherapy approaches to fabricate and utilize nanoparticles for cancer therapy. These phototherapy approaches, such as photothermal therapy (PTT) and photodynamic therapy (PDT), hold great promise to overcome the limitations of traditional treatment methods. In phototherapy, magnetic iron oxide nanoparticles (IONPs) are of paramount importance due to their wide range of biomedical applications. This review discusses the basic concepts, various therapy approaches (PTT, PDT, magnetic hyperthermia therapy (MHT), chemotherapy and immunotherapy), intrinsic properties, and mechanisms of cell death of IONPs; it also provides a brief overview of recent developments in IONPs, with focus on their therapeutic applications. Much attention is devoted to elaborating the various parameters, intracellular behaviors and limitations of MHT. Bimodal therapies which act alone or in combination with other modalities are also discussed. The review highlights some limitations in the explored research areas and suggests future directions to overcome these limitations.

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