Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jul;40(7):1408-18.
doi: 10.1007/s10439-012-0550-3. Epub 2012 Mar 27.

2011 Rita Schaffer lecture: nanoparticles for intracellular nucleic acid delivery

Jordan J Green  1
Affiliations

2011 Rita Schaffer lecture: nanoparticles for intracellular nucleic acid delivery

Jordan J Green. Ann Biomed Eng. 2012 Jul.

Abstract

Nanoparticles are a promising technology for delivery of new types of therapeutics. A polymer library approach has allowed engineering of polymeric particles that are particularly effective for the delivery of DNA and siRNA to human cells. Certain chemical structural motifs, degradable linkages, hydrophobicity, and biophysical properties are key for successful intracellular delivery. Small differences to biomaterial structure, and especially the type of degradable linkage in the polymers, can be critical for successful delivery of siRNA vs. DNA. Furthermore, subtle changes to biomaterial structure can facilitate cell-type gene delivery specificity between human brain cancer cells and healthy cells as well as between human retinal endothelial cells and epithelial cells. These polymeric nanoparticles are effective for nucleic acid delivery in a broad range of human cell types and have applications to regenerative medicine, ophthalmology, and cancer among many other biomedical research areas.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Gene delivery mechanism. Reproduced with permission from: Sunshine, Bishop, & Green, Therapeutic Delivery 2011 Volume 2, Issue 4, pp. 493–521.
Figure 2
Figure 2
Monomer structures and polymer synthesis. The polymer library consists of polymers synthesized by the combination of 9 backbone monomers “B”, 5 side chain monomers “S”, and 11 end-group monomers “E.”
Figure 3
Figure 3
Increased hydrophobicity improves gene delivery of LUC DNA to COS-7 cells. Average log-scale luminescence post-transfection (mean±s.e) of end-modified polymers with the same base polymer. Reproduced with permission from: Sunshine et al., Biomacromolecules 2011 Volume 12, Issue 10, pp. 3592–600.
Figure 4
Figure 4
Biomaterial structure mediates cell-specific delivery. (A) Polymeric nanoparticles preferentially transfect brain tumor stem cells (BTSC) rather than fetal neural stem cells (NSCs). Reproduced with permission from . (B) Polymeric nanoparticles highly effective for transfection of macrovasculature (HUVEC) are also highly effective for transfection of microvasculature (HREC). Reproduced with permission from . All cells were transfected with GFP DNA and measured by flow cytometry.
See this image and copyright information in PMC

References

    1. American Cancer Society. Cancer facts and figures. 2005. Cancer facts and figures 2012: American Cancer Society.
    1. Gene therapy clinical trials worldwide. J Gene Medicine. 2012
    1. Acharya S, Sahoo SK. PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect. Adv Drug Delivery Rev. 2011;63(3):170–183. - PubMed
    1. Anderson DG, Lynn DM, Langer R. Semi-automated synthesis and screening of a large library of degradable cationic polymers for gene delivery. Angew Chem Int Ed. 2003;42:3153–3158. - PubMed
    1. Arote RB, Jiang HL, Kim YK, Cho MH, Choi YJ, Cho CS. Degradable poly(amido amine)s as gene delivery carriers. Expert Opin Drug Deliv. 2011;8(9):1237–1246. - PubMed

Publication types