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 |
