Nanomaterials for mRNA-based therapeutics: Challenges and opportunities.

Messenger RNA (mRNA) holds great potential in developing immunotherapy, protein replacement, and genome editing. In general, mRNA does not have the risk of being incorporated into the host genome and does not need to enter the nucleus for transfection, and it can be expressed even in nondividing cells. Therefore, mRNA-based therapeutics provide a promising strategy for clinical treatment. However, the efficient and safe delivery of mRNA remains a crucial constraint for the clinical application of mRNA therapeutics. Although the stability and tolerability of mRNA can be enhanced by directly retouching the mRNA structure, there is still an urgent need to improve the delivery of mRNA. Recently, significant progress has been made in nanobiotechnology, providing tools for developing mRNA nanocarriers. Nano-drug delivery system is directly used for loading, protecting, and releasing mRNA in the biological microenvironment and can be used to stimulate the translation of mRNA to develop effective intervention strategies. In the present review, we summarized the concept of emerging nanomaterials for mRNA delivery and the latest progress in enhancing the function of mRNA, primarily focusing on the role of exosomes in mRNA delivery. Moreover, we outlined its clinical applications so far. Finally, the key obstacles of mRNA nanocarriers are emphasized, and promising strategies to overcome these obstacles are proposed. Collectively, nano-design materials exert functions for specific mRNA applications, provide new perception for next-generation nanomaterials, and thus revolution of mRNA technology.

Lipid oxidation stability of ultra-high-temperature short-time sterilization sporoderm-broken pine pollen (UHT-PP) and 60 Co-irradiation sterilization sporoderm-broken pine pollen (60 Co-PP).

BACKGROUND: Pine pollen, a kind of Chinese traditional medicine, is rich in unsaturated fatty acids. During its processing, it is often needed to break the sporoderm in order to increase the availability of some ingredients, which can cause lipid oxidation and the development of rancidity during storage. RESULTS: The primal peroxide value (PV) of ultra-high-temperature short-time sterilization sporoderm-broken pine pollen (UHT-PP) was much higher (over 15 times) than raw pine pollen (R-PP) and 60 Co-irradiation sterilization sporoderm-broken pine pollen (60 Co-PP). The PV of UHT-PP first increased and then decreased shortly after; however, PV of R-PP and 60 Co-PP remained almost unchanged during storage. The volatiles associated with rancidity in UHT-PP were found to be significantly higher than 60 Co-PP, especially hexanal (nearly 30 times) and hexanoic acid (about 2 times), and a multi-organoleptic sensor analyzer (electronic nose system) was able to differentiate these three kinds of samples when the output was subjected to discriminant function analysis. During storage (30 days), hexanal first increased and then decreased (at about 5 days), and hexanoic acid continuously increased for UHT-PP; however, no significant change was noted for R-PP or 60 Co-PP. UHT-PP has a greater surface area than 60 Co-PP, although same sporoderm-broken processes were applied. Antioxidants (flavone, carotenoid and tocopherols, sterol compounds) in 60 Co-PP were significantly (P ≤ 0.05, by Duncan's multiple range test) higher than that in UHT-PP, although not significantly different for total phenolics. CONCLUSIONS: Rancidity occurs more readily in UHT-PP than in R-PP and 60 Co-PP during storage, probably because significant lipid oxidation and antioxidant degradation occurred during the UHT sterilization sporoderm-broken processing of pine pollen. © 2018 Society of Chemical Industry.

Crosslinked Aspartic Acids as Helix-Nucleating Templates.

Described is a facile helix-nucleating template based on a tethered aspartic acid at the N-terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side-chain-end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N-terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix-stabilizing methods.