Abstract |
Folate-targeted liposomes (FTL) were tested as drug delivery vehicles to PSMA-positive cancer cells. We used FL with co-entrapped mitomycin C lipophilic prodrug (MLP) and doxorubicin (DOX), and the LNCaP prostate cancer cell line which expresses PSMA but is negative for folate receptor. A major increase in cell drug levels was observed when LNCaP cells were incubated with FTL as compared to non-targeted liposomes (NTL). MLP was activated to mitomycin C, and intracellular and nuclear fluorescence of DOX was detected, indicating FTL processing and drug bioavailability. PMPA (2-(phosphonomethyl)-pentanedioic acid), a specific inhibitor of PSMA, blocked the uptake of FTL into LNCaP cells, but did not affect the uptake of FTL into PSMA-deficient and folate receptor-positive KB cells. The cytotoxic activity of drug-loaded FTL was found significantly enhanced when compared to NTL in LNCaP cells. FTL may provide a new tool for targeted therapy of cancers that over-express the PSMA receptor.
|
Authors | Yogita Patil, Hilary Shmeeda, Yasmine Amitay, Patricia Ohana, Saran Kumar, Alberto Gabizon |
Journal | Nanomedicine : nanotechnology, biology, and medicine
(Nanomedicine)
Vol. 14
Issue 4
Pg. 1407-1416
(06 2018)
ISSN: 1549-9642 [Electronic] United States |
PMID | 29680672
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2018 Elsevier Inc. All rights reserved. |
Chemical References |
- Antigens, Surface
- Liposomes
- Mitomycin
- Doxorubicin
- Folic Acid
- FOLH1 protein, human
- Glutamate Carboxypeptidase II
|
Topics |
- Antigens, Surface
(metabolism)
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Doxorubicin
(chemistry, pharmacology)
- Drug Delivery Systems
(methods)
- Folic Acid
(chemistry)
- Glutamate Carboxypeptidase II
(metabolism)
- Humans
- Liposomes
(chemistry)
- Male
- Mitomycin
(chemistry, pharmacology)
- Prostatic Neoplasms
(metabolism)
|