Lipid Polymer Hybrid Nanomaterials for mRNA Delivery


Authors: W Zhao, C Zhang, B Li, X Zhang, X Luo, C Zeng, W Li, M Gao, Y Dong

Journal: Cellular and Molecular Bioengineering

DOI: 10.1007/s12195-018-0536-9

Publication - Abstract

October 01, 2018

Abstract

Introduction:

In the past decade, messenger RNA (mRNA) has been extensively explored in a wide variety of biomedical applications. However, efficient delivery of mRNA is still one of the key challenges for its broad applications in the clinic. Recently, lipid polymer hybrid nanoparticles (LPNs) are evolving as a promising class of biomaterials for RNA delivery, which integrate the physicochemical properties of both lipids and polymers. We previously developed an N1,N3,N5-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide (TT) derived lipid-like nanomaterial (TT3-LLN) which was capable of effectively delivering multiple types of mRNA. In order to further improve the delivery efficiency of TT3-LLN, in this study, we focused on studying the effects of incorporating different polymers on establishing LPNs and aimed to develop an optimized lipid polymer hybrid nanomaterial for efficient mRNA delivery. 

Methods:

We incorporated a series of biodegradable and biocompatible polymer materials into the formulation of TT3-LLNs to develop LPNs. mRNA delivery efficiency of different LPNs were evaluated and a systematic orthogonal optimization was further carried out. 

Results:

Our data indicated that PLGA4 (MW 24,000–38,000 g/mol) dramatically increased delivery efficiency of TT3-LLNs in comparison to other polymers. Further optimization identified PLGA4-7 LPNs (PLGA:mRNA = 9:1, mass ratio; TT3:DOPE:Cholesterol:DMG-PEG2000 = 25:25:45:0.75, molar ratio) as a lead formulation, which displayed significantly enhanced delivery of two types of mRNA in three different human cell lines as compared with TT3-LLNs. 

Conclusions:

Results from this study potentially provide new insights into developing LPNs for mRNA based therapeutics.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Blog Posts
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
  • Blaze
    • Cartridges
    • Another Child
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads
  • Spark
    • Cartridges


related content

Publication - Abstract

The therapeutic applications of lipid nanoparticle (LNP) formulations of small interfering RNA (siRNA), are hampered by inefficient delivery of encapsulated siRNA to the cytoplasm following endocytosis.

Read More


Publication - Abstract

Knockdown of Anillin Actin Binding Protein Blocks Cytokinesis in Hepatocytes and Reduces Liver Tumor Development in Mice without Affecting Regeneration

Zhang S, Nguyen LH, Zhou K, Tu H, Sehgal A, Nassour I, Li L, Purva Gopal, Goodman J, Singal AG, Yopp A, Zhang Y, Siegwart DJ, Zhu H

Cytokinesis can fail during normal postnatal liver development, leading to polyploid hepatocytes. We investigated whether inhibiting cytokinesis in the liver slows tumor growth without compromising the health of normal hepatocytes. We inhibited cyt...

Read More


Stay Informed

Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.

MENU
X