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

Published

September 29, 2021

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

Pub Type

Journals

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 April 19, 2024)