Abstract
A gene delivery system was designed to carry a payload to integrin overexpressing cells. Branched-polyethyleneimine (bPEI) condensed plasmid DNA was encapsulated into targeted stealth liposomes, thereby combining the condensing and transfection properties of bPEI with the stealth and targeting properties of the liposomal carrier system. PR-b was used as a targeting ligand-a peptide we designed to bind specifically to the cancer cell surface marker α5β1 integrin-and such a robust receptor-ligand interaction achieved higher specificity than what has been previously reported for targeted delivery systems. In the process of formulating the PR-b functionalized gene delivery vehicle, we developed a protocol to fully encapsulate condensed DNA in liposomes and accurately quantify the total DNA in the system. We demonstrate that compared to non-targeted stealth liposomes and non-encapsulated condensed DNA, the PR-b functionalized stealth liposomes mediated improved in vitro transfection specifically to colon cancer cells overexpressing the α5β1 integrin. Furthermore, when administered in vivo to metastatic tumor bearing mice, PR-b functionalized stealth liposomes outperformed non-targeted liposomes and delivered genes specifically to the tumor site.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 393-401 |
| Number of pages | 9 |
| Journal | Biomaterials Science |
| Volume | 1 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2013 |
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PR-b functionalized stealth liposomes for targeted delivery to metastatic colon cancer. / Adil, Maroof; Belur, Lalitha; Pearce, Timothy R.; Levine, Rachel M.; Tisdale, Alison W.; Sorenson, Brent S.; Mc Ivor, R S; Kokkoli, Efrosini.
In: Biomaterials Science, Vol. 1, No. 4, 01.04.2013, p. 393-401.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - PR-b functionalized stealth liposomes for targeted delivery to metastatic colon cancer
AU - Adil, Maroof
AU - Belur, Lalitha
AU - Pearce, Timothy R.
AU - Levine, Rachel M.
AU - Tisdale, Alison W.
AU - Sorenson, Brent S.
AU - Mc Ivor, R S
AU - Kokkoli, Efrosini
PY - 2013/4/1
Y1 - 2013/4/1
N2 - A gene delivery system was designed to carry a payload to integrin overexpressing cells. Branched-polyethyleneimine (bPEI) condensed plasmid DNA was encapsulated into targeted stealth liposomes, thereby combining the condensing and transfection properties of bPEI with the stealth and targeting properties of the liposomal carrier system. PR-b was used as a targeting ligand-a peptide we designed to bind specifically to the cancer cell surface marker α5β1 integrin-and such a robust receptor-ligand interaction achieved higher specificity than what has been previously reported for targeted delivery systems. In the process of formulating the PR-b functionalized gene delivery vehicle, we developed a protocol to fully encapsulate condensed DNA in liposomes and accurately quantify the total DNA in the system. We demonstrate that compared to non-targeted stealth liposomes and non-encapsulated condensed DNA, the PR-b functionalized stealth liposomes mediated improved in vitro transfection specifically to colon cancer cells overexpressing the α5β1 integrin. Furthermore, when administered in vivo to metastatic tumor bearing mice, PR-b functionalized stealth liposomes outperformed non-targeted liposomes and delivered genes specifically to the tumor site.
AB - A gene delivery system was designed to carry a payload to integrin overexpressing cells. Branched-polyethyleneimine (bPEI) condensed plasmid DNA was encapsulated into targeted stealth liposomes, thereby combining the condensing and transfection properties of bPEI with the stealth and targeting properties of the liposomal carrier system. PR-b was used as a targeting ligand-a peptide we designed to bind specifically to the cancer cell surface marker α5β1 integrin-and such a robust receptor-ligand interaction achieved higher specificity than what has been previously reported for targeted delivery systems. In the process of formulating the PR-b functionalized gene delivery vehicle, we developed a protocol to fully encapsulate condensed DNA in liposomes and accurately quantify the total DNA in the system. We demonstrate that compared to non-targeted stealth liposomes and non-encapsulated condensed DNA, the PR-b functionalized stealth liposomes mediated improved in vitro transfection specifically to colon cancer cells overexpressing the α5β1 integrin. Furthermore, when administered in vivo to metastatic tumor bearing mice, PR-b functionalized stealth liposomes outperformed non-targeted liposomes and delivered genes specifically to the tumor site.
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U2 - 10.1039/c2bm00128d
DO - 10.1039/c2bm00128d
M3 - Article
VL - 1
SP - 393
EP - 401
JO - Biomaterials Science
JF - Biomaterials Science
SN - 2047-4830
IS - 4
ER -