Dual-targeting superparamagnetic iron oxide nanoprobes with high and low target density for brain glioma imaging
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Keywords:
Nanoprobe
Superparamagnetism
Folate receptor
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Iron oxide nanoparticles
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An electrochemical, label-free method was developed to detect folate receptor positive tumor cells by specific recognition of a polydopamine-coated carbon nanotubes-folate nanoprobe to cell-surface folate receptors. This strategy offers great promise to extend its application in studying the interaction of ligand and cell-surface receptor.
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Hydrogen peroxide is a biologically important reactive oxygen species (ROS) and plays crucial roles in living organisms. Herein, a FRET-based ratiometric fluorescent probe has been developed for detecting H2O2in vitro and in vivo. In this nanoprobe, carbon dots serve as the energy donor and carrier for the H2O2 recognition element. This nanoprobe exhibits fast-response, low toxicity, high sensitivity (with a detection limit of 0.5 μM) and selectivity towards H2O2 over other reactive oxygen or nitrogen species. The nanoprobe has been successfully applied in the detection of H2O2 in live cells and in zebrafish larvae. By incubating the nanoprobe with zebrafishes, the nanoprobe can be absorbed by the fishes within 1 h and accumulates mainly in the abdominal region. Due to its small size (∼4 nm), the nanoprobe is gradually excreted by zebrafishes without long-term accumulation. Moreover, as the first ratiometric chemoprobe that can detect H2O2in vivo, the nanoprobe has been found capable of detecting and locating endogenous H2O2 in zebrafishes as a result of drug-induced oxidative damage. The successful detection of H2O2 by the nanoprobe in vivo may support its eventual use in clinical applications.
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Abstract Background: Excellent imaging performance and good biocompatibility of contrast agents are considered as prerequisites for accurate tumor diagnosis and treatment. Results: Herein, a novel imaging nanoprobe with actively targeting performance based on ultrasmall paramagnetic iron oxide (USPIO) was constructed by a facile cation exchange strategy followed by conjugation with transferrin (Tf). The stable gadolinium (Gd 3+ ) chelation endows the nanoparticles (NPs) with a low value of r 2 /r 1 (1.28) and relatively high r 1 value of 3.2 mM -1 s -1 , enabling their use in T 1 -weighted positive MR imaging. Conclusion: This constructed transferrin modified gadolinium-iron chelate nanoprobe, named as TUG, shows high biocompatibility within a given dose range. More importantly, compared with clinically used Gd-based small molecule contrast agents, the obtained TUG can be more engulfed by breast cancer cells, showing much enhanced T 1 -weighted positive MR imaging in either subcutaneous or in situ tumor models of breast cancer. This novel nanoprobe holds enormous promise to be utilized as a targeting contrast agent with high efficacy for T 1 -weighted positive MR imaging.
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Cu2+ is closely related to the occurrence and development of Wilson's disease (WD), and quantitative detection of various copper indicators (especially liver Cu2 and urinary Cu2+) is the key step for the early diagnosis of WD in the clinic. However, the clinic Cu2+ detection approach was mainly based on testing the liver tissue through combined invasive liver biopsy and the ICP-MS method, which is painful for the patient and limited in determining WD status in real-time. Herein, we rationally designed a type of Cu2+-activated nanoprobe based on nanogapped gold nanoparticles (AuNNP) and poly(N-isopropylacrylamide) (PNIPAM) to simultaneously quantify the liver Cu2+ content and urinary Cu2+ in WD by photoacoustic (PA) imaging and ratiometric surface-enhanced Raman scattering (SERS), respectively. In the nanoprobe, one Raman molecule of 2-naphthylthiol (NAT) was placed in the nanogap of AuNNP. PNIPAM and the other Raman molecule mercaptobenzonitrile (MBN) were coated on the AuNNP surface, named AuNNP-NAT@MBN/PNIPAM. Cu2+ can efficiently coordinate with the chelator PNIPAM and lead to aggregation of the nanoprobe, resulting in the absorption red-shift and increased PA performance of the nanoprobe in the NIR-II window. Meanwhile, the SERS signal at 2223 cm–1 of MBN is amplified, while the SERS signal at 1378 cm–1 of NAT remains stable, generating a ratiometric SERS I2223/I1378 signal. Both NIR-II PA1250 nm and SERS I2223/I1378 signals of the nanoprobe show a linear relationship with the concentration of Cu2+. The nanoprobe was successfully applied for in vivo quantitative detection of liver Cu2+ of WD mice through NIR-II PA imaging and accurate quantification of urinary Cu2+ of WD patients by ratiometric SERS. We anticipate that the activatable nanoprobe might be applied for assisting an early, precise diagnosis of WD in the clinic in the future.
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The present study describes a systematic approach towards the design and development of novel, bio-functionalized, magneto-fluorescent nanoparticles for cancer-specific targeting. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl or aldehyde groups, to be later used for bio-conjugation, were designed using an aminophosphonic acid coupling agent. These magneto-fluorescent nanoparticles were further functionalized with folic acid, using diverse conjugation strategies. A series of new iron-oxide folate nanoconjugates with excellent aqueous dispersion stability and reasonably good hydrodynamic sizes under a wide range of physiological conditions were developed. These ultradispersed nanosystems were analyzed for their physicochemical properties and cancer-cell targeting ability, facilitated by surface modification with folic acid. The nanoparticle size, charge, surface chemistry, magnetic properties and colloidal stability were extensively studied using a variety of complementary techniques. Confocal microscopy, performed with folate receptor positive human cervical HeLa cancer cells, established that these non-cytotoxic iron-oxide folate nanoconjugates were effectively internalized by the target cells through receptor-mediated endocytosis. Cell-uptake behaviors of nanoparticles, studied using magnetically activated cell sorting (MACS), clearly demonstrated that cells over-expressing the human folate receptor internalized a higher level of these nanoparticle-folate conjugates than negative control cells.
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We report a new type of dual modal nanoprobe to combine optical and magnetic resonance bioimaging. A simple reverse microemulsion method and coating process was introduced to synthesize silica-coated Gd2(CO3)3:Tb nanoparticles, and the particles, with an average diameter of 16 nm, can be dispersed in water. As in vitro cell imaging of the nanoprobe shows, the nanoprobe accomplishes delivery to gastric SGC7901 cancer cells successfully in a short time, as well as NCI-H460 lung cancer cells. Furthermore, it presents no evidence of cell toxicity or adverse affect on kidney cell growth under high dose, which makes the nanoprobe's optical bioimaging modality available. The possibility of using the nanoprobe for magnetic resonance imaging is also demonstrated, and the nanoprobe displays a clear T1-weighted effect and could potentially serve as a bimodal T1-positive contrast agent. Therefore, the new nanoprobe formed from carbonate nanoprobe doped with rare earth ions provides the dual modality of optical and magnetic resonance imaging.
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