Journal article
Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy
ACS applied materials & interfaces, Vol.13(38), pp.45244-45258
09/29/2021
DOI: 10.1021/acsami.1c11981
PMID: 34524806
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-
-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.
Details
- Title: Subtitle
- Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy
- Creators
- Aniket Wahane - University of ConnecticutShipra Malik - University of ConnecticutKuo-Chih Shih - University of ConnecticutRavinder Reddy Gaddam - University of IowaChaohao Chen - University of ConnecticutYun Liu - NIST Center for Neutron ResearchMu-Ping Nieh - University of ConnecticutAjit Vikram - University of IowaRaman Bahal - University of Connecticut
- Resource Type
- Journal article
- Publication Details
- ACS applied materials & interfaces, Vol.13(38), pp.45244-45258
- DOI
- 10.1021/acsami.1c11981
- PMID
- 34524806
- ISSN
- 1944-8244
- eISSN
- 1944-8252
- Grant note
- name: NATIONAL INSTITUTE OF HEALTH
- Language
- English
- Date published
- 09/29/2021
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359948602771
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