Dextran-coated superparamagnetic iron oxide nanoparticles (DSPIONs) have gained considerable interest, because of their biocompatibility and biosafety in clinics. Doxorubicin (Dox), a widely used chemotherapeutic drug, always has limited applications in clinical therapy due to its serious side effects of dose-limiting irreversible cardiotoxicity and myelo suppression. Herein, DSPIONs were synthesized and developed as magnetic carriers for doxorubicin. The Dox-DSPION conjugates were evaluated in the in vitro test of Dox release, which showed pH-dependence with the highest release percentage of 50.3% at pH 5.0 and the lowest release percentage of 11.8% in a physiological environment. The cytotoxicity of DSPIONs and Dox-DSPIONs evaluated by the MTT assay indicated that DSPIONs had no cytotoxicity and the conjugates had significantly reduced the toxicity (IC50 = 1.36 μg mL(-1)) compared to free Dox (IC50 = 0.533 μg mL(-1)). Furthermore, confocal microscopic data of cell uptake suggest that less cytotoxicity of Dox-DSPIONs may be attributed to the cellular internalization of the conjugates and sustainable release of Dox from the formulation in the cytoplasm. More importantly, the results from the rabbit VX2 liver tumor model test under an external magnetic field showed that the conjugates had approximately twice the anti-tumor activity and two and a half times the animal survival rate, respectively, compared to free Dox. Collectively, our data have demonstrated that Dox-DSPIONs have less toxicity with better antitumor effectiveness in in vitro and in vivo applications, suggesting that the conjugates have potential to be developed into chemo-therapeutic formulations.
Fe3O4/Au (GoldMag) particles with core/shell structure were synthesized by reduction of Au3+ with hydroxylamine in the presence of Fe3O4. The synthesized particles have an average size smaller than 100 nm in diameter with of superparemagnetic properties due to their Fe oxide cores. The particles show optical features with a plasmon resonance peak from 550, 570 to 590 nm correlating with increasing diameters from 50 nm, 70 nm to 100 nm. The GoldMag particles need only a single step for antibody immobilization and have high binding capacity for antibodies. These advantages permit improved methods of isolating and detecting biomolecules.
Immediate response for disease control relies on simple, inexpensive, and sensitive diagnostic tests, highly sought after for timely and accurate test of various diseases, including infectious diseases. Composite Fe3O4/Au nanoparticles have attracted considerable interest in diagnostic applications due to their unique physical and chemical properties. Here, we developed a simple coating procedure for gold magnetic nanoparticles (GMNs) with poly(acrylic acid) (PAA). PAA-coated GMNs (PGMNs) were stable and monodispersed and characterized by Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy, UV-visible scanning spectrophotometry, thermogravimetric analysis, and Zetasizer methodologies. For diagnostic application, we established a novel lateral flow immunoassay (LFIA) strip test system where recombinant Treponema pallidum antigens (r-Tp) were conjugated with PGMNs to construct a particle probe for detection of anti-Tp antibodies. Intriguingly, the particle probes specifically identified Tp antibodies with a detection limitation as low as 1 national clinical unit/mL (NCU/mL). An ample pool of 1020 sera samples from three independent hospitals were obtained to assess our PGMNs-based LFIA strips, which exhibited substantially high values of sensitivity and specificity for all clinical tests (higher than 97%) and, therefore, proved to be a suitable approach for syphilis screening at a point-of-care test manner.
Single nucleotide polymorphisms (SNPs) are closely related to genetic diseases, but current SNP detection methods, such as DNA microarrays that include tedious procedures and expensive, sophisticated instruments, are unable to perform rapid SNPs detection in clinical practice, especially for those multiple SNPs related to genetic diseases. In this study, we report a sensitive, low cost, and easy-to-use point-of-care testing (POCT) system formed by combining amplification refractory mutation system (ARMS) polymerase chain reaction with gold magnetic nanoparticles (GMNPs) and lateral flow assay (LFA) noted as the ARMS-LFA system, which allow us to use a uniform condition for multiple SNPs detection simultaneously. The genotyping results can be explained by a magnetic reader automatically or through visual interpretation according to the captured GMNPs probes on the test and control lines of the LFA device. The high sensitivity (the detection limit of 0.04 pg/μL with plasmid) and specificity of this testing system were found through genotyping seven pathogenic SNPs in phenylalanine hydroxylase gene ( PAH, the etiological factor of phenylketonuria). This system can also be applied in DNA quantification with a linear range from 0.02 to 2 pg/μL of plasmid. Furthermore, this ARMS-LFA system was applied to clinical trials for screening the seven pathogenic SNPs in PAH of 23 families including 69 individuals. The concordance rate of the genotyping results detected by the ARMS-LFA system was up to 97.8% compared with the DNA sequencing results. This method is a very promising POCT in the detection of multiple SNPs caused by genetic diseases.
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