Cytoplasmic delivery of functional siRNA using pH-Responsive nanoscale hydrogels

William B. Liechty, Rebekah L. Scheuerle, Julia E. Vela Ramirez, Nicholas Peppas

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The progress of short interfering RNA (siRNA) technologies has unlocked the development of novel alternatives for the treatment of a myriad of diseases, including viral infections, autoimmune disorders, or cancer. Nevertheless, the clinical use of these therapies faces significant challenges, mainly overcoming the charged and large nature of these molecules to effectively enter the cell. In this work, we developed a cationic polymer nanoparticle system that is able to load siRNA due to electrostatic interactions. The pH-responsiveness and membrane-disrupting ability of these carriers make them suitable intracellular delivery vehicles. In the work presented herein we synthesized, characterized, and evaluated the properties of nanoparticles based on 2-diethylaminoethyl methacrylate and tert-butyl methacrylate copolymers. A disulfide crosslinker was incorporated in the nanogels to enable the degradation of the nanoparticles in reductive environments, showing no significant changes on their physicochemical properties. The capability of the developed nanogels to be internalized, deliver siRNA, and induce gene knockdown were demonstrated using a human epithelial colorectal adenocarcinoma cell line. Overall, these findings suggest that this platform exhibits desirable characteristics as a potential siRNA-delivery platform.

Original languageEnglish (US)
Pages (from-to)249-257
Number of pages9
JournalInternational journal of pharmaceutics
Volume562
DOIs
StatePublished - May 1 2019

Fingerprint

Hydrogels
Small Interfering RNA
Nanoparticles
Gene Knockdown Techniques
Virus Diseases
Static Electricity
Disulfides
Polymers
Adenocarcinoma
Technology
Cell Line
Membranes
Neoplasms
NanoGel
Therapeutics

Keywords

  • Cationic
  • Drug delivery
  • Intracellular
  • Nanoparticles
  • Polymer
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Cytoplasmic delivery of functional siRNA using pH-Responsive nanoscale hydrogels. / Liechty, William B.; Scheuerle, Rebekah L.; Vela Ramirez, Julia E.; Peppas, Nicholas.

In: International journal of pharmaceutics, Vol. 562, 01.05.2019, p. 249-257.

Research output: Contribution to journalArticle

Liechty, William B. ; Scheuerle, Rebekah L. ; Vela Ramirez, Julia E. ; Peppas, Nicholas. / Cytoplasmic delivery of functional siRNA using pH-Responsive nanoscale hydrogels. In: International journal of pharmaceutics. 2019 ; Vol. 562. pp. 249-257.
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