Conjugate Polyplexes with Anti-Invasive Properties and Improved siRNA Delivery in Vivo

Yi Chen, Jing Li, David Oupicky

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

This study reports on a simple method to prepare siRNA-polycation conjugate polyplexes by in situ thiol-disulfide exchange reaction. The conjugate polyplexes are prepared using thiol-terminated siRNA and a bioreducible branched polycationic inhibitor of the CXCR4 chemokine receptor (rPAMD). The rPAMD-SS-siRNA conjugate polyplexes exhibit improved colloidal stability and resistance against disassembly with heparin, serum, and physiological salt concentrations when compared with control conventional rPAMD/siRNA polyplexes. Coating the polyplexes with human serum albumin masks the positive surface charge and contributes to the enhanced in vitro gene silencing and improved safety in vivo. The conjugate polyplexes display improved in vivo reporter gene silencing following intravenous injection in tumor-bearing mice. Because the conjugate polyplexes retained the ability of rPAMD to inhibit CXCR4 and restrict cancer cell invasion, the developed systems show promise for future combination anti-metastatic siRNA therapies of cancer.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalBioconjugate Chemistry
Volume29
Issue number2
DOIs
StatePublished - Feb 21 2018

Fingerprint

Small Interfering RNA
Bearings (structural)
Genes
Surface charge
Tumors
Masks
Gene Silencing
Sulfhydryl Compounds
Display devices
Cells
Salts
Coatings
CXCR4 Receptors
Neoplasms
Chemokine Receptors
Reporter Genes
Serum Albumin
Intravenous Injections
Disulfides
Heparin

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Conjugate Polyplexes with Anti-Invasive Properties and Improved siRNA Delivery in Vivo. / Chen, Yi; Li, Jing; Oupicky, David.

In: Bioconjugate Chemistry, Vol. 29, No. 2, 21.02.2018, p. 296-305.

Research output: Contribution to journalArticle

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