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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
Pub Type
Journals
Keywords
sans nanoparticles, cytoplasmic delivery, histidine
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 October 1, 2025)