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A colonic drug delivery system was developed to specifically deliver 5-aminosalicylic acid (5-ASA) to the inflamed site by conjugating with hemoglobin nanoparticles (HbNPs). The 5-ASA-HbNPs (eight 5-ASA molecules per Hb molecule) with the size of 220 nm and zeta potential of -14.6 mV is a tailored nanoparticle able to pass through the mucus layer. The 5-ASA-HbNPs do not undergo chemical and enzymatic hydrolysis in the simulated gastrointestinal fluids over 6 h. Significantly higher cellular uptakes and prolonged release was seen for the 5-ASA-HbNPs in Caco-2 cells, compared to free 5-ASA over 72 h. In addition, 5-ASA-HbNPs revealed similar therapeutic effectiveness with free 5-ASA against tumor necrosis factor and showed less inhibitory concentration (IC50) for myeloperoxidase enzyme activity. In vivo imaging of mouse demonstrated the localization of drug in the descending colon after oral administration and about 15% of the administered dose was recovered as 5-ASA from urine in 6 h. The use of these nanoparticles with the mucus adhesion properties and permeability to intestinal epithelial cells can be a good candidate with potential application in the colonic drug delivery field.

Template-mediated self-assembly synthesis has produced a diverse range of biomimetic materials with unique physicochemical properties. Here, we fabricated novel fluorescent three-dimensional (3-D) hydroxyapatite (HAP) nanorod-assembled microspheres using iron quantum cluster (FeQC) as a hybrid template, containing three organic components: hemoglobin chains, piperidine, and iron clusters. The material characterization indicated that the synthesized HAP possessed a uniform rod-like morphology, ordered 3-D architecture, high crystallinity, self-activated fluorescence, and remarkable photostability. Our study proposed that this FeQC template is a promising regulating agent to fabricate fluorescent self-assembled HAP microspheres with a controlled morphology. The effect of HAP on stem cell fate and their osteogenic differentiation was investigated by culturing human bone marrow-derived mesenchymal stromal/stem cells (BMSCs) with HAP microspheres. Significant increases in collagen matrix production and gene expression of osteogenic markers, including osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), bone sialoprotein (BSP) and alkaline phosphatase (ALP), were observed compared to the controls after 21 days of culture. Taken together, our data suggest that synthetic HAP nanorod-assembled microspheres represent a promising new biomaterial which exhibits enhanced fluorescent properties and osteoinductive effects on human BMSCs.

A new method based on fluorescent probe of iron quantum cluster has been proposed for rapid detection of Escherichia coli (E. coli). The iron quantum cluster was synthesized using hemoglobin as both a source of iron and a protective agent (Hb-FeQCs). The investigation of the sensitivity of Hb-FeQCs towards metal ions showed a highly selective turn off fluorescence for Cu2+. It suggests that Cu2+ can induce fluorescence quenching by binding to amino acids of Hb. The ability of E. coli bacteria to capture and reduce of Cu ions caused to efficient recovery of the fluorescence of Hb-FeQCs from Cu2+-caused quenching. This probe has a satisfactorily linear range of 0.35–35 μM for Cu2+ under the optimal iron quantum cluster concentration (500 μg/mL) with an 85 nM detection limit. Rapid and facile detection of E.coli bacteria with the limit of detection around 8.3 × 103 CFU/mL was successfully achieved in the artificially contaminated urine, tap water, and DMEM samples within 30 min. The fluorescence recovery was investigated by different types of bacteria and only E. coli revealed 56% recovery which related to its capability to Cu2+ reduction and the great potential of the fluorescent probe for rapid detection of pathogenic E. coli bacteria. Furthermore, the Hb-FeQCs can detect E. coli bacteria in an infected urine sample by retrieving up to 74% of its fluorescence which is helpful to accelerate the diagnosis and treatment of urinary tract infection (UTI).

The authors describe a novel water-soluble, stable, biocompatible, and highly fluorescent probe consisting of iron quantum clusters incorporated into human adult hemoglobin (Hb-FeQCs). The Hb-FeQCs were characterized by various spectroscopic techniques. The probe displays strong absorption and yellow fluorescence with a peak centered at 567 nm (photo-excited at 460 nm). The Hb-FeQCs show excellent photostability over a wide range of pH values (5–12), even in the presence of high electrolyte concentrations. A colorimetric and a fluorometric method were worked out for the quantitation Zn(II) and cysteine in aqueous solution. Zinc ions induce a visible color change from brown to yellow. The sensitivity of Hb-FeQCs towards other metal ions was negligible, with the exception of Co2+ and Cu2+, which caused a modest interference. The Hb-FeQCs were exploited in a sensitive and selective turn-on fluorescence assay for Zn2+. It is also found that cysteine quenches the fluorescence of the Hb-FeQCs/Zn(II) complex. Under the optimized conditions, the probe has a linear response in the 0.04 to 2.2 μM Zn(II) concentration range, with a 48 nM detection limit. Response to cysteine is linear in the 1–60 μM concentration range, with a 0.25 μM limit of detection. This fluorescent probe undergoes fluorescent emission intensity enhancement upon binding to zinc ions in living normal human fibroblast cells under visible lamp. The cellular imaging capability and very low cytotoxicity of this soluble iron quantum clusters can be potentially extended as an exciting sub-nanoplatform with promising biomaterial applications.