Development of T1/T2 dual-mode MRI contrast
agents that can also treat cancer is an attractive prospect for personalized
precision medicine. Unfortunately, conventional contrast agents can
suffer from toxicity and lack any ability to treat cancer. An all-iron
T1/T2 MR imaging agent with photothermal and
drug delivery capability would overcome these issues. Here, an avocado-like
Fe3+/Fe2O3 composed T1-T2 dual-mode contrast agent based on Fe-TA coordination
network (CNMN) is developed. This material possesses suitable longitudinal
and transverse relaxation coefficients. Moreover, the strong heat
generation property of Fe-TA endows CNMN with the capability to act
as a potent photothermal agent. Furthermore, CNMN can also act as
an effective delivery platform for the chemotherapeutic drug doxorubicin
(DOX) to achieve high effective chemo-photothermal combination therapy.
The work demonstrates reliable T1-T2 MRI-guided
chemo-photothermal therapy for safe and effective clinical application.
Designing a smart nanotheranostic system has recently attracted tremendous attention and is highly desirable for realizing targeted cancer therapy and early diagnosis. Herein we report the fabrication of smart nanotheranostic system using multiresponsive gatekeeping protocol of mesoporous silica nanoparticles (MSN). Acid, oxidative stress and redox sensitive manganese oxide (MnO ) coated superparamagnetic iron oxide nanoparticle (SPION) were employed as nanolids to regulate the camptothecin drug release from the channels of mesoporous silica and achieve responsive dual-mode MRI contrast. The nonvehicle showed high magnetization and T2 contrast in magnetic resonance imaging (MRI) due to the significant density of SPION onto the surface of MSN, and at the same time the MnO shell degradation release Mn which enhanced the T1MRI visualization. The efficacy of responsive drug delivery system was investigated on pancreatic cancer cells and tumor-bearing mice, and results reinforced that MnO -SPION@MSN@CPT nonvehicle is efficacious against cancer cells. We envision that our unique and multiresponsive nanoplatform may find applications in effective delivering of imaging and therapeutic agents to wide range of diseases besides cancer.
As an important recycling and degradation system, autophagy is considered to be critical in regulating stem cell differentiation. It has been shown that graphene oxide quantum dots (GOQDs) are a robust biological labelling tool for stem cells with little cytotoxicity. In this study,
we explored the role of autophagy in regulating the impact of GOQDs on the odontoblastic differentiation of DPSCs during autophagy. Western blotting and immunofluorescence staining were used to evaluate the autophagic activity of DPSCs. Quantitative PCR, alizarin red S staining, and alkaline
phosphatase staining were used to examine DPSC odontoblastic differentiation. The impacts of ROS scavengers on autophagy induction and reactive oxygen species (ROS) levels were also measured. Lentiviral vectors carrying Beclin1 siRNA sequences, as well as autophagy inhibitors (3-MA and bafilomycin
A1), were used to inhibit autophagy. Initial exposure to GOQDs increased autophagic activity and enhanced DPSC mineralization. Autophagy inhibition suppressed GOQD-induced odontoblastic differentiation. Moreover, GOQD treatment induced autophagy in a ROS-dependent manner. GOQDs promoted differentiation,
which could be modulated via ROS-induced autophagy.
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