Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges

Extracellular vesicles (EVs) comprise apoptotic bodies, microvesicles and exosomes, and they perform as key regulators in cell-to-cell communication in normal as well as diseased states. EVs contain natural cargo molecules, such as miRNA, mRNA and proteins, and transfer these functional cargos to neighboring cells or more distant cells through circulation. These functionally active molecules then affect distinct signaling cascades. The message conveyed to the recipient cells is dependent upon the composition of the EV, which is determined by the parent cell and the EV biogenesis. Because of their properties such as increased stability in circulation, biocompatibility, low immunogenicity and toxicity, EVs have drawn attention as attractive delivery systems for therapeutics. This review focuses on the functional use of exosomes in therapy and the potential advantages and challenges in using exosomes for therapeutic purposes.

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Exosomes: new molecular targets of diseases

Extracellular vesicles: Novel promising delivery systems for therapy of brain diseases.

The present study reports, novel and greener method for synthesis of gold nanoparticles (AuNPs) using 5,7-dihydroxy-6-metoxy-3',4'methylenedioxyisoflavone (Dalspinin), isolated from the roots of Dalbergia coromandeliana was carried out for the first time. The synthesized gold nanoparticles were characterized by UV-Vis spectroscopy, high resolution transmission electron microscopy (HR-TEM), selected area electron diffraction (SAED), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The observed surface plasmon resonance (SPR) at 532nm in the UV-Vis absorption spectrum indicates the formation of gold nanoparticles. The powder XRD and SAED pattern for synthesized gold nanoparticles confirms crystalline nature. The HR-TEM images showed that the AuNPs formed were small in size, highly monodispersed and spherical in shape. The average particle sizes of the AuNPs are found to be ~10.5nm. The prepared AuNPs were found to be stable for more than 5months without any aggregation. The catalytic degradation studies of the synthesized AuNPs towards degradation of congo red and methyl orange, showed good catalytic in the complete degradation of both the dyes. The reduction catalyzed by gold nanoparticles followed the pseudo-first order kinetics, with a rate constant of 4.5×10-3s-1 (R2=0.9959) and 1.7×10-3s-1 (R2=0.9918) for congo red (CR) and methyl orange (MO), respectively.

Green synthesis, characterization and catalytic degradation studies of gold nanoparticles against congo red and methyl orange.

The present study takes advantage of the beneficial effects of resveratrol as a neuroprotective compound. Resveratrol-loaded solid lipid nanoparticles were functionalized with apolipoprotein E which can be recognized by the LDL receptors overexpressed on the blood–brain barrier. Transmission electron microscopy images revealed spherical nanoparticles, dynamic light scattering gave a Z-average lower than 200 nm, and a zeta potential of around −13 mV and very high resveratrol entrapment efficiency (ca. 90 %). In vitro cytotoxic effects were assessed by MTT and LDH assays in hCMEC/D3 cell line and revealed no toxicity up to 50 μM over 4 h of incubation. The permeability through hCMEC/D3 monolayers showed a significant increase (1.8-fold higher) for resveratrol-loaded solid lipid nanoparticles functionalized with apolipoprotein E when compared to non-functionalized ones. In conclusion, these nanosystems might be a promising strategy for resveratrol delivery into the brain, while protecting it from degradation in the blood stream.

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Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E

Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals.

Four vegetable oils with typical fatty acid compositions were chosen to determine their indicators of lipid oxidation under the conditions of accelerated oxidation. Good linear correlations were observed between the total nonpolar carbonyl amount and the total oxidation value (TOTOX, R2 = 0.89–0.97) or peroxide value (POV, R2 = 0.92–0.97) during 35 days of accelerated oxidation. Additionally, nonanal in camellia oil (oleic acid mainly) increased significantly, and correlated linearly with TOTOX (21.6 TOTOX – 595, R2 = 0.92); propanal increased significantly in perilla oil (linolenic acid mainly) and correlated linearly with TOTOX (8.10 TOTOX + 75.0, R2 = 0.90). Hexanal (9.56 TOTOX + 913, R2 = 0.90, and 7.10 TOTOX + 342, R2 = 0.78, respectively) and nonenal (10.5 TOTOX + 691, R2 = 0.95, and 6.65 TOTOX + 276, R2 = 0.84, respectively) in sunflower oil (linoleic acid mainly) and palm oil (palmitic and oleic acids mainly) also had good linear correlations with TOTOX. Considering the change patterns of these fo...

Novel approach to evaluate the oxidation state of vegetable oils using characteristic oxidation indicators

Analysis of nonpolar lipophilic aldehydes/ketones in oxidized edible oils using HPLC-QqQ-MS for the evaluation of their parent fatty acids.

Oxidative stabilities represented with variance of fatty acids, tocopherols, acid value, peroxide value, and thiobarbituric acid value of edible vegetable oils with limited air were investigated. The total tocopherol contents were positively correlated with the polyunsaturated fatty acids (PUFA, r2 = 0.856), negatively correlated with the monounsaturated fatty acids (MUFA, r2 = −0.598), and saturated fatty acids (SFA, r2 = −0.258) in initial oxidation. The residual contents of tocopherols had good negative linear correlations with the peroxide value and thiobarbituric acid value during oxidation. When α-tocopherol predominated over other homologue, it presented a pro-oxidant effect at high concentration, but would transform to be an antioxidant as its concentration decreased to the inflection point that corresponded to the inflection point of peroxide value increase for different kinds of vegetable oils. However, the γ- or δ-tocopherol did not show pro-oxidant action. Therefore, the influence of α-tocophe...

https://www.tandfonline.com/doi/pdf/10.1080/10942912.2013.864674

Jun Cao

Papers

Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals.

Novel approach to evaluate the oxidation state of vegetable oils using characteristic oxidation indicators

Analysis of nonpolar lipophilic aldehydes/ketones in oxidized edible oils using HPLC-QqQ-MS for the evaluation of their parent fatty acids.

Effect of Fatty Acid and Tocopherol on Oxidative Stability of Vegetable Oils with Limited Air

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.