| TI:
|
Title
Rerouting lipoprotein nanoparticles to selected
alternate receptors for the targeted delivery of
cancer diagnostic and therapeutic agents |
| AU:
|
Author
Zheng, Gang; Chen, Juan; Li, Hui; Glickson, Jerry
D |
| AF:
|
Author Affiliation
Department of Radiology, University of
Pennsylvania School of Medicine, Philadelphia, PA
19104 |
| SO:
|
Source
Proceedings of the National Academy of Sciences,
USA [Proc. Natl. Acad. Sci. USA]. Vol. 102, no.
49, pp. 17757-17762. 6 Dec 2005. |
| IS:
|
ISSN
0027-8424 |
| EI:
|
Electronic ISSN
1091-6490 |
| DE:
|
Descriptors
Lipoproteins; Folic acid; Lipoproteins (low
density); Cancer; imaging; nanoparticles; Lipids;
Apolipoprotein B; lipoprotein receptors; Confocal
microscopy; photodynamic therapy; Drug delivery |
| AB:
|
Abstract
We report that a lipoprotein-based nanoplatform
generated by conjugating tumor-homing molecules to
the protein components of naturally occurring
lipoproteins reroutes them from their normal
lipoprotein receptors to other selected
cancer-associated receptors. Multiple copies of
these targeting moieties may be attached to the
same nanoparticle, or a variety of different
targeting moieties can be attached. Such a diverse
set of tumor-homing molecules could be used to
create a variety of conjugated lipoproteins as
multifunctional, biocompatible nanoplatforms with
a broad application to both cancer imaging and
treatment. The same principle can be applied to
imaging and treatment of other diseases and for
monitoring specific tissues. To validate this
concept, we prepared a low-density lipoprotein (LDL)-based
folate receptor (FR)-targeted agent by conjugating
folic acid to the Lys residues of the
apolipoprotein B (apoB)-100 protein. To
demonstrate the ability of the lipoprotein-based
nanoplatform to deliver surfaceloaded and
core-loaded payloads, the particles were labeled
either with the optical reporter
1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocya
nine that was intercalated in the phospholipid
monolayer or with the lipophilic photodynamic
therapy agent, tetra-t-butyl-silicon
phthalocyanine bisoleate, that was reconstituted
into the lipid core. Cellular localization of the
labeled LDL was monitored by confocal microscopy
and flow cytometry in FR-overexpressing KB cells,
in FR-nonexpressing CHO and HT-1080 cells, and in
LDL receptor-overexpressing HepG sub(2) cells.
These studies demonstrate that the folic acid
conjugation to the Lys side-chain amino groups
blocks binding to the normal LDL receptor and
reroutes the resulting conjugate to cancer cells
through their FRs. |
| LA:
|
Language
English |
| SL:
|
Summary Language
English |
| PY:
|
Publication Year
2005 |
| PT:
|
Publication Type
Journal Article |
| CL:
|
Classification
W3 33388 Drug delivery vehicles (liposomes,
cochleates, microspheres) |
| UD:
|
Update
200603 |
| SF:
|
Subfile
Medical and Pharmaceutical Biotechnology Abstracts
|
| AN:
|
Accession Number
6578563 |
| PG:
|
Journal Pages
17757-17762 |
| JV:
|
Journal Volume
102 |
| JI:
|
Journal Issue
49 |
