Smart Design of Nanomaterials for Mitochondria-Targeted Nanotherapeutics.

Mitochondria are the powerhouse of cells. They are vital organelles that maintain cellular function and metabolism. Dysfunction of mitochondria results in various diseases with a great diversity of clinical appearances. In the past, strategies have been developed for fabricating subcellular-targeting drug-delivery nanocarriers, enabling cellular internalization and subsequent organelle localization. Of late, innovative strategies have emerged for the smart design of multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade and overcome various barriers encountered upon in vivo administration to reach the organelle with good bioavailability. Stimuli-responsive nanocarriers allow controlled release of therapeutics to occur at the desired target site. Synergistic therapy can be achieved using a combination of approaches such as chemotherapy, gene and phototherapy. In this Review, we survey the field for recent developments and strategies used in the smart design of nanocarriers for mitochondria-targeted therapeutics. Existing challenges and unexplored therapeutic opportunities are also highlighted and discussed to inspire the next generation of mitochondrial-targeting nanotherapeutics.

Is "nano safe to eat or not"? A review of the state-of-the art in soft engineered nanoparticle (sENP) formulation and delivery in foods.

With superior physicochemical properties, soft engineered nanoparticles (sENP) (protein, carbohydrate, lipids and other biomaterials) are widely used in foods. The preparation, functionalities, applications, transformations in gastrointestinal (GI) tract, and effects on gut microbiota of sENP directly incorporated for ingestion are reviewed herein. At the time of this review, there is no notable report of safety concerns of these nanomaterials found in the literature. Meanwhile, various beneficial effects have been demonstrated for the application of sENP. To address public perception and safety concerns of nanoscale materials in food, methodologies for evaluation of physiological effects of nanomaterials are reviewed. The combination of these complementary methods will be useful for the establishment of a comprehensive risk assessment system.

PVP- coated naringenin nanoparticles for biomedical applications - In vivo toxicological evaluations.

Naringenin (NAR) is one of the naturally occurring flavonoids found in citrus fruits and exerts a wide variety of pharmacological activities. The clinical relevance of naringenin is limited by its low solubility and minimal bioavailability, owing to its largely hydrophobic ring structure. The aim of the present study is to develop a novel naringenin nanoparticle system (NAR NP) using simple nanoprecipitation technique with polyvinylpyrrolidone (PVP) as the hydrophilic carrier. The synthesized nanoparticles were characterized using XRD, FTIR, SEM and EDX. The characterization study revealed the nanoscale properties and the interactions between NAR and PVP. In vivo toxicological evaluations were carried out at various doses (1, 5, 10 & 50 mg/kg body wt) in male Sprague-Dawley rats in comparison with silver nanoparticle (AgNP) at toxic concentration (50 mg/kg body wt). The altered hepatotoxicity markers, hematology parameters and antioxidant defense system were observed in AgNP- treated rats. But NAR NP - treated rats did not show any biochemical alterations and improved the antioxidant defense indices when compared to control group, by virtue of the pharmacological properties exerted by NAR. The modulatory effect of NAR NP over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and heart reinforce our findings. These studies provide preliminary answers to some of the key biological issues raised over the use and safety of nanoparticles for diagnostic and therapeutic applications. Consequently, we suggest that the safe NAR NP can be used to reduce the dosage of NAR, improve its bioavailability and merits further investigation for therapeutic applications.

Transcription MRI: a new view of the living brain.

Altered gene activities are underlying causes of many neurological disorders. The ability to detect, image, and report endogenous gene transcription using magnetic resonance (MR) holds great potential for providing significant clinical benefits. In this review, we present the development of conjugates consisting of gene-targeting short nucleic acids (oligodeoxynucleotides, or sODN) and superparamagnetic iron oxide nanoparticles (SPION, an MR susceptibility T(2) agent) for reporting gene activity using transcription MRI (tMRI). We will discuss 1) the target specificity of sODN, 2) selection of contrast agents for tMRI, 3) the distribution and uptake, 4) sequence specificity, 5) histology of SPION and sODN, 6) data acquisition and quantitative analysis for tMRI, and 7) application of gene transcript-targeting nanoparticles in biology and medicine. We will also discuss methods of validating the correlation between results from conventional assays (in situ hybridization, PCR, histology Prussian blue stain and immunohistochemistry) in postmortem samples and retention of SPION-sODN using tMRI. The application of our novel contrast probe to report and target gene transcripts in the mesolimbic pathways of living mouse brains after amphetamine exposure will be discussed. Because of the targeting ability in the nucleic acid sequence, the concept of tMRI probes with complementary nucleic acid (antisense DNA or short interfering RNA) allows not only tracking, targeting, binding to intracellular mRNA, and manipulating gene action but also tracing cells with specific gene action in living brains. Transcription MRI will lend itself to myriad applications in living organs.