Next Article in Journal
The Effects of Hybridization on the Flexural Performances of Carbon/Glass Interlayer and Intralayer Composites
Next Article in Special Issue
Soy-Based Soft Matrices for Encapsulation and Delivery of Hydrophilic Compounds
Previous Article in Journal
Properties and Fabrication of PA66/Surface-Modified Multi-Walled Nanotubes Composite Fibers by Ball Milling and Melt-Spinning
Previous Article in Special Issue
Design, Synthesis and Architectures of Hybrid Nanomaterials for Therapy and Diagnosis Applications
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Polymers 2018, 10(5), 548; https://doi.org/10.3390/polym10050548

Molecular Weight-Dependent Activity of Aminated Poly(α)glutamates as siRNA Nanocarriers

1
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Room 607, Tel Aviv University, Tel Aviv 69978, Israel
2
School of Chemistry, the Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel Aviv 69978, Israel
3
Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA
*
Author to whom correspondence should be addressed.
Received: 25 April 2018 / Revised: 14 May 2018 / Accepted: 15 May 2018 / Published: 20 May 2018
(This article belongs to the Special Issue Polymers for Therapy and Diagnostics)
Full-Text   |   PDF [4224 KB, uploaded 20 May 2018]   |  

Abstract

RNA interference (RNAi) can contribute immensely to the area of personalized medicine by its ability to target any gene of interest. Nevertheless, its clinical use is limited by lack of efficient delivery systems. Polymer therapeutics can address many of the challenges encountered by the systemic delivery of RNAi, but suffer from inherent drawbacks such as polydispersity and batch to batch heterogeneity. These characteristics may have far-reaching consequences when dealing with therapeutic applications, as both the activity and the toxicity may be dependent on the length of the polymer chain. To investigate the consequences of polymers’ heterogeneity, we have synthesized two batches of aminated poly(α)glutamate polymers (PGAamine), differing in their degree of polymerization, but not in the monomer units or their conjugation. Isothermal titration calorimetry study was conducted to define the binding affinity of these polymers with siRNA. Molecular dynamics simulation revealed that Short PGAamine:siRNA polyplexes exposed a higher amount of amine moieties to the surroundings compared to Long PGAamine. This resulted in a higher zeta potential, leading to faster degradation and diminished gene silencing. Altogether, our study highlights the importance of an adequate physico-chemical characterization to elucidate the structure–function-activity relationship, for further development of tailor-designed RNAi delivery vehicles. View Full-Text
Keywords: polyplexes; siRNA delivery; physico-chemical characterization; cationic polymer; anticancer therapy; poly(α)glutamate polyplexes; siRNA delivery; physico-chemical characterization; cationic polymer; anticancer therapy; poly(α)glutamate
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Krivitsky, A.; Krivitsky, V.; Polyak, D.; Scomparin, A.; Eliyahu, S.; Gibori, H.; Yeini, E.; Pisarevsky, E.; Blau, R.; Satchi-Fainaro, R. Molecular Weight-Dependent Activity of Aminated Poly(α)glutamates as siRNA Nanocarriers. Polymers 2018, 10, 548.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Polymers EISSN 2073-4360 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top