Abstract
The efficacy of many therapeutic molecules could be greatly enhanced by polymer-based nanoparticle systems capable of delivering them to the direct vicinity of the cell nucleus. However, degradation of the particles and encapsulated drugs within the enzyme-rich and low-pH environments of the endo/lysosomal pathway of cells has dramatically limited the efficacy of such systems. In this paper, we discovered that small polymeric particles (42 nm) enter live cells via a novel mechanism that leads to trafficking outside the endo/lysosomal pathway. Sub-25 nm particles rapidly transport to the perinuclear region of cells in vesicles that never acidify. The pathway is non-degradative, cholesterol independent, and non-clathrin and non-caveolae mediated. This privileged non-acidic pathway may be general since our results are surprisingly obtained with standard latex polymer beads without addition of ligands and may, therefore, provide a promising route for drug and gene delivery using biomaterial-based nanodevices.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2876-2884 |
| Number of pages | 9 |
| Journal | Biomaterials |
| Volume | 28 |
| Issue number | 18 |
| DOIs | |
| State | Published - 2007 |
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Keywords
- Gene delivery
- Intracellular delivery
- Non-caveolae
- Non-clathrin
- Size
- Trafficking
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biomedical Engineering
Cite this
Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway. / Lai, Samuel K.; Hida, Kaoru; Man, Stan T.; Chen, Clive; Machamer, Carolyn E; Schroer, Trina A.; Hanes, Justin S.
In: Biomaterials, Vol. 28, No. 18, 2007, p. 2876-2884.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway
AU - Lai, Samuel K.
AU - Hida, Kaoru
AU - Man, Stan T.
AU - Chen, Clive
AU - Machamer, Carolyn E
AU - Schroer, Trina A.
AU - Hanes, Justin S
PY - 2007
Y1 - 2007
N2 - The efficacy of many therapeutic molecules could be greatly enhanced by polymer-based nanoparticle systems capable of delivering them to the direct vicinity of the cell nucleus. However, degradation of the particles and encapsulated drugs within the enzyme-rich and low-pH environments of the endo/lysosomal pathway of cells has dramatically limited the efficacy of such systems. In this paper, we discovered that small polymeric particles (42 nm) enter live cells via a novel mechanism that leads to trafficking outside the endo/lysosomal pathway. Sub-25 nm particles rapidly transport to the perinuclear region of cells in vesicles that never acidify. The pathway is non-degradative, cholesterol independent, and non-clathrin and non-caveolae mediated. This privileged non-acidic pathway may be general since our results are surprisingly obtained with standard latex polymer beads without addition of ligands and may, therefore, provide a promising route for drug and gene delivery using biomaterial-based nanodevices.
AB - The efficacy of many therapeutic molecules could be greatly enhanced by polymer-based nanoparticle systems capable of delivering them to the direct vicinity of the cell nucleus. However, degradation of the particles and encapsulated drugs within the enzyme-rich and low-pH environments of the endo/lysosomal pathway of cells has dramatically limited the efficacy of such systems. In this paper, we discovered that small polymeric particles (42 nm) enter live cells via a novel mechanism that leads to trafficking outside the endo/lysosomal pathway. Sub-25 nm particles rapidly transport to the perinuclear region of cells in vesicles that never acidify. The pathway is non-degradative, cholesterol independent, and non-clathrin and non-caveolae mediated. This privileged non-acidic pathway may be general since our results are surprisingly obtained with standard latex polymer beads without addition of ligands and may, therefore, provide a promising route for drug and gene delivery using biomaterial-based nanodevices.
KW - Gene delivery
KW - Intracellular delivery
KW - Non-caveolae
KW - Non-clathrin
KW - Size
KW - Trafficking
UR - http://www.scopus.com/inward/record.url?scp=33947580368&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947580368&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2007.02.021
DO - 10.1016/j.biomaterials.2007.02.021
M3 - Article
C2 - 17363053
AN - SCOPUS:33947580368
VL - 28
SP - 2876
EP - 2884
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 18
ER -