The ability to deliver medicines and genetic materials into a cell can be a powerful tool to treat disease. Recently, researchers at University of Connecticut and University of Iowa purchased PLGA from PolySciTech (www.polyscitech.com) to create poly(histidine)-PLGA mixed nanoparticles. They researched the use of this as a way to deliver nanoparticles into cells. This research holds promise to improve intracellular delivery. Read more: Wahane, Aniket, Shipra Malik, Kuo-Chih Shih, Ravinder Reddy Gaddam, Chaohao Chen, Yun Liu, Mu-Ping Nieh, Ajit Vikram, and Raman Bahal. "Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c11981
“Abstract: Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, an excessive positive charge density often leads to severe cell and tissue-based toxicity that restricts the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of cationic poly(lactic-co-glycolic acid) (PLGA)-histidine-based nanoformulations for enhanced cytoplasmic delivery with minimal toxicity. PLGA/poly-l-histidine nanoparticles show promising physico-biochemical features and transfection efficiency in a series of in vitro and cell culture-based studies. Further, the use of acetone/dichloromethane as a solvent mixture during the formulation process significantly improves the morphology and size distribution of PLGA/poly-l-histidine nanoparticles. PLGA/poly-l-histidine nanoformulations undergo clathrin-mediated endocytosis. A contrast-matched small-angle neutron scattering experiment confirmed poly-l-histidine’s distribution on the PLGA nanoformulations. PLGA/poly-l-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-155 as nucleic acid analog are efficacious in in vitro and in vivo studies. PLGA/poly-l-histidine NPs significantly decrease tumor growth in PNA-155 (∼6 fold) and paclitaxel (∼6.5 fold) treatment groups in a lymphoma cell line derived xenograft mice model without inducing any toxicity. Hence, PLGA/poly-l-histidine nanoformulations exhibit substantial transfection efficiency and are safe to deliver reagents ranging from small molecules to synthetic nucleic acid analogs and can serve as a novel platform for drug delivery. KEYWORDS: poly-l-histidine PLGA nanoparticles proton-sponge effect microRNAs”
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