Discovery of a Peptoid-Based Nanoparticle Platform for Therapeutic mRNA Delivery via Diverse Library Clustering and Structural Parametrization.

Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform. First, we identify a promising peptoid structural motif by clustering a library of >200 molecules based on predicted physical properties and evaluate members of each cluster for reporter gene expression in vivo. Then, the lead peptoid motif is optimized using design of experiments methodology to explore variations on the charged and lipophilic portions of the peptoid, facilitating the discovery of trends between structural elements and nanoparticle properties. We further demonstrate that peptoid-based Nutshells leads to expression of therapeutically relevant levels of an anti-respiratory syncytial virus antibody in mice with minimal tolerability concerns or induced immune responses compared to benchmark ionizable lipid, DLin-MC3-DMA. Through this work, we present peptoid-based nanoparticles as a tunable delivery platform that can be optimized toward a range of therapeutic programs.

First record of plastiglomerates, pyroplastics and plasticrusts along the beaches of Tamilnadu, Southeast coast of India.

Plastic litter affects coastal and marine ecosystems globally. This study represents the first record of pyroplastics and plasticrust in the beaches of Tamil Nadu, India. All samples were FTIR spectroscopically examined to confirm the polymer composition of the suspected plastics. The 16 plastic formations were found in TamilNadu, including six plastiglomerates nine pyroplastics and one plasticrust. Five types of polymers (PET, PP, PVC, PA, and PE) were found on the plastic matrices. The study also revealed that pyroplastics and plasticrust formed by degradation of plastics through weathering in the coastal environment. The present study also found that four types of marine fouling organisms such as oyster larvae, bryozoan, barnacle and polychaete worm were encrusted on the two pyroplastics. The emergence of these new forms of plastic raises concerns about their interactions with the environment and biota.