pH‐Activatable MnO‐Based Fluorescence and Magnetic Resonance Bimodal Nanoprobe for Cancer Imaging

Abstract

Stimuli-responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH-activatable fluorescence/MRI dual-modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin-545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high-specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over-express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin-545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor-mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn(2+) ions thus released are also shown to exert a strong T1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual-activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer-imaging modalities such as image-guided cancer therapy.

Targeted Magnetic Resonance Imaging and Modulation of Hypoxia with Multifunctional Hyaluronic Acid‐MnO2 Nanoparticles in Glioma

“…In our study, HA‐MnO 2 NPs after induced by exposure to H 2 O 2 or GSH in acidic environment attained much higher r 1 relaxivity than that of commercial CA, for example, Gd‐DPTA ( r 1 = 3.5 mM −1 s −1 ). In addition, the r 1 and r 2 relaxivities of HA‐MnO 2 NPs induced by exposure to H 2 O 2 or GSH in acidic environment were higher than or similar to other MnO 2 ‐based NPs previously reported . It has been reported that r 1 relaxivity of MnO 2 can increase in various tumor environments, such as low pH (5.0–6.8), high H 2 O 2 , and high GSH .…”

“…In addition, the r 1 and r 2 relaxivities of HA‐MnO 2 NPs induced by exposure to H 2 O 2 or GSH in acidic environment were higher than or similar to other MnO 2 ‐based NPs previously reported . It has been reported that r 1 relaxivity of MnO 2 can increase in various tumor environments, such as low pH (5.0–6.8), high H 2 O 2 , and high GSH . Thus, MnO 2 is considered as a novel, activatable tumor environment‐responsive CA for MRI.…”

“…and/or external triggers (magnetic/electronic field, ultrasound, light, etc.). These properties allow MnO 2 ‐based MRI to sense biochemical activities, increase the target‐to‐background ratio of MnO 2 ‐based MRI, and improve its imaging accuracy and sensitivity for cancer detection and diagnosis . To date, direct reducing potassium permanganate (KMnO 4 ) with a reducing agent, such as cationic poly‐(allylamine hydrochloride) (PAH) to form MnO 2 nanoparticles (MnO 2 NPs) has become one of the most preferred methods .…”

Assembly of Au Plasmonic Photothermal Agent and Iron Oxide Nanoparticles on Ultrathin Black Phosphorus for Targeted Photothermal and Photodynamic Cancer Therapy

“…The researchers have already explored many methods to enhance the accuracy and efficiency of selective localization in the course of treatment, such as magnetic targeting, molecular targeting, imaging‐guidance, and so on. In particular, the magnetic targeting, which can be achieved by the involvement of iron oxide nanoparticles in the treatment platform, can not only get the physical position of drugs but also realize the imaging (MRI) guided therapy effect simultaneously . Notably, another advantage of magnetic targeting over molecular targeting methods is no dependency on the specific receptor expression (such as the receptor expression variation in normal tissues, or the patient‐to‐patient differentiation) .…”

Recent Progress on Manganese‐Based Nanostructures as Responsive MRI Contrast Agents

“…[64] Ad ifferent strategy towards complex nanostructures is the co-encapsulation of the different components (including preformed MnO x )i nside polymericorl ipid matrices ( Figure 2D). [32,44] In general terms, the preparation of well-defined manganese oxidesn anostructures other than MnO 2 requires more complex approaches. For example, Hsu et al [44] reported the preparation of MnO NPs through the thermal decomposition of manganese(II)o leatea t2 80 8Cf or 1h.T hermal decomposition protocols are based on the controlled destruction of organometallic compounds in oxygen-and water-free atmosphere,r esulting in the slow availability of metal precursors, thus enabling close [41] B) Fe 3 O 4 @Mn 3 O 4 nanoparticles, [42] C) MnO@Mn 3 O 4 nanoparticles, [43] D) MnO@SiO 2 nanoparticles, [44] E) hollow MnO 2 nanoparticles, [45] F) Fe 3 O 4 /MnO x -GO nanostructures.…”