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Dual-Modality Poly-^dL-Histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy

Published

Author(s)

Aniket Wahane, Shipra Malik, Kuo-Chih Shih, Ravinder R. Gaddam, Chaohao Chen, Yun Liu, Mu-Ping Neih, Ajit Vikram, Raman Bahal

Abstract

Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, excess of positive charge often leads to severe cell and tissue-based toxicity that restrict the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of poly-(lactic-co-glycolic acid) (PLGA)-histidine based nanoformulations containing cationic charge for enhanced cytoplasmic delivery with minimal toxicity. We performed comprehensive physico-biochemical characterizations including dynamic light scattering, loading analysis, release kinetics and cellular uptake studies using confocal and flow cytometry-based methods on coumarin dye-containing PLGA-histidine formulations. We established that PLGA-poly-L-histidine nanoparticles show superior transfection efficiency compared to other PLGA-histidine and conventional PLGA formulations. Further, we noted that using acetone:dichloromethane as a solvent mixture during the formulation process significantly improves the morphology uniformity, size, and size distribution of the PLGA-poly-L-histidine nanoparticles. Our results substantiated that PLGA-poly-L-histidine nanoformulations undergo clathrin-mediated endocytosis without causing any severe toxicity. Contrast matched small-angle neutron scattering experiments was performed to confirm poly-L-histidine's distribution on the nanoformulations. Further, for proof of principle, PLGA-poly-L-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-210 as nucleic acid analog were tested for functional studies. Hence, we established that PLGA-poly-L-histidine nanoformulations possess superior transfection efficiency to deliver reagents ranging from small molecules to nucleic acid analogs and serve as a novel platform for drug delivery.
Citation
ACS Applied Materials and Interfaces
Volume
13
Issue
38

Keywords

sans nanoparticles, cytoplasmic delivery, histidine

Citation

Wahane, A. , Malik, S. , Shih, K. , Gaddam, R. , Chen, C. , Liu, Y. , Neih, M. , Vikram, A. and Bahal, R. (2021), Dual-Modality Poly-^dL-Histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy, ACS Applied Materials and Interfaces (Accessed June 5, 2023)
Created September 28, 2021, Updated November 29, 2022