Iron Oxide Nanoparticle-Mediated mRNA Delivery to Hard-to-Transfect Cancer Cells.

mRNA-based therapeutics have emerged as a promising strategy for cancer treatment. However, the effective delivery of mRNA into hard-to-transfect cancer cells remains a significant challenge. This study introduces a novel approach that utilizes iron oxide nanoparticles (NPs) synthesized through a layer-by-layer (LbL) method for safe and efficient mRNA delivery. The developed NPs consist of an iron oxide core modified with a thin charge-bearing layer, an mRNA middle layer, and an outer layer composed of perfluorinated polyethyleneimine with heparin (PPH), which facilitates efficient mRNA delivery. Through a comparative analysis of four nanoparticle delivery formulations, we investigated the effects of the iron oxide core's surface chemistry and surface charge on mRNA complexation, cellular uptake, and mRNA release. We identified an optimal and effective mRNA delivery platform, namely, (IOCCP)-mRNA-PPH, capable of transporting mRNA into various hard-to-transfect cancer cell lines in vitro. The (IOCCP)-mRNA-PPH formulation demonstrated significant enhancements in cellular internalization of mRNA, facilitated endosomal escape, enabled easy mRNA release, and exhibited minimal cytotoxicity. These findings suggest that (IOCCP)-mRNA-PPH holds great promise as a solution for mRNA therapy against hard-to-transfect cancers.

The development of a guide to borderline orthodontic need.

OBJECTIVE: To produce a guide for dentists and orthodontists to determine orthodontic treatment need in borderline cases (dental health component DHC 3) and to compare views of different panels of judges on treatment need. MATERIALS AND METHODS: Prospective, observational study. Photographs of one hundred subjects displaying borderline occlusal traits (DHC3) were collected. Three panels of judges consisting of 25 orthodontists, 25 dentists and 25 lay persons assessed photographs based on orthodontic treatment need on aesthetic grounds. RESULTS: Spearman's correlation coefficient showed no statistical difference between the panels of judges (p < 0.001). The judges identified a 'high need' for treatment on aesthetic grounds for those with anterior open bites and reverse overjets. Kappa analysis showed moderate intra-rater agreement for the orthodontic and dental panels of judges (k = 0.47 and 0.45, respectively) and fair agreement (k = 0.26) for the lay panel, highlighting the intrinsic difficulty of assessing borderline malocclusions. CONCLUSION: There was no statistical difference in the way the orthodontic, dental and lay panels of judges perceived treatment need for DHC 3 cases. Anterior open bites and reverse overjets were predominantly found to be in high need of treatment by all panels of judges. A 'Guide to Borderline Orthodontic Need' (GBON) is proposed consisting of 8 photographs of subjects with borderline occlusal traits (DHC3) determined unambiguously by lay, dental and orthodontic panels as either 'needing' or 'not needing' orthodontic treatment on aesthetic grounds. It is anticipated that this will assist users to make judgments on aesthetic grounds on the need for treatment in borderline cases.