MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent

Purpose

Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser.

Procedures

The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX.

Results

Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 μg/ml in 1 W/cm² 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT.

Conclusion

MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.

     

Bio-aerosols in indoor environment: composition, health effects and analysis

Bio-aerosols are airborne particles that are living (bacteria, viruses and fungi) or originate from living organisms. Their presence in air is the result of dispersal from a site of colonization or growth. The health effects of bio-aerosols including infectious diseases, acute toxic effects, allergies and cancer coupled with the threat of bioterrorism and SARS have led to increased awareness on the importance of bio-aerosols. The evaluation of bio-aerosols includes use of variety of methods for sampling depending on the concentration of microorganisms expected. There have been problems in developing standard sampling methods, in proving a causal relationship and in establishing threshold limit values for exposures due to the complexity of composition of bio-aerosols, variations in human response to their exposure and difficulties in recovering microorganisms. Currently bio-aerosol monitoring in hospitals is carried out for epidemiological investigation of nosocomial infectious diseases, research into airborne microorganism spread and control, monitoring biohazardous procedures and use as a quality control measure. In India there is little awareness regarding the quality of indoor air, mould contamination in indoor environments, potential source for transmission of nosocomial infections in health care facilities. There is an urgent need to undertake study of indoor air, to generate baseline data and explore the link to nosocomial infections. This article is a review on composition, sources, modes of transmission, health effects and sampling methods used for evaluation of bio-aerosols, and also suggests control measures to reduce the loads of bio-aerosols.     

Socio-environmental predictors of Barmah forest virus transmission in coastal areas, Queensland, Australia

Objective  To assess the socio-environmental predictors of Barmah forest virus (BFV) transmission in coastal areas, Queensland, Australia.
Methods  Data on BFV notified cases, climate, tidal levels and socioeconomic index for area (SEIFA) in six coastal cities, Queensland, for the period 1992–2001 were obtained from the relevant government agencies. Negative binomial regression models were used to assess the socio-environmental predictors of BFV transmission.
Results  The results show that maximum and minimum temperature, rainfall, relative humidity, high and low tide were statistically significantly associated with BFV incidence at lags 0–2 months. The fitted negative binomial regression models indicate a significant independent association of each of maximum temperature (β = 0.139, P  = 0.000), high tide (β = 0.005, P  = 0.000) and SEIFA index (β = −0.010, P  = 0.000) with BFV transmission after adjustment for confounding variables.
Conclusions  The transmission of BFV disease in Queensland coastal areas seemed to be determined by a combination of local social and environmental factors. The model developed in this study may have applications in the control and prevention of BFV disease in these areas.     

Acrodermatitis enteropathica-like skin eruption in a case of short bowel syndrome following jejuno-transverse colon anastomosis

Acrodermatitis enteropathica is a rare autosomal recessive disorder of zinc deficiency. Zinc is an essential trace element in human metabolism and acquired zinc deficiency may manifest with skin eruptions simulating acrodermatitis enteropathica. We report an unusual case of acrodermatitis enteropathica-like skin eruption due to deficiency of zinc and other nutritional factors in a patient who has undergone extensive small bowel resection and jejuno-transverse colon anastomosis for mesenteric ischemia.     

Silicon-based fluorescent platforms for copper(ii) detection in water

The potential of silicon-based fluorescent platforms for the detection of trace toxic metal ions was investigated in an aqueous environment. To this aim, silicon chips were first functionalized with amino groups, and fluorescein organic dyes, used as sensing molecules, were then covalently linked to the surface via formation of thiourea groups. The obtained hybrid heterostructures exhibited high sensitivity and selectivity towards copper(ii), a limit of detection compatible with the recommended upper limits for copper in drinking water, and good reversibility using a standard metal–chelating agent. The fluorophore–analyte interaction mechanism at the basis of the reported fluorescence quenching, as well as the potential of performance improvement, were also studied. The herein presented sensing architecture allows, in principle, tailoring of the selectivity towards other metal ions by proper fluorophore selection, and provides a favorable outlook for integration of fluorescent chemosensors with silicon photonics technology.

Covalent linkage of fluorescein to silanized silicon chips yields solid-state platforms for detection of copper(ii) in water. This architecture represents a step forward towards the fabrication of sensors for remote water analysis applications.