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Targeting of folate-conjugated liposomes with co-entrapped drugs to prostate cancer cells via prostate-specific membrane antigen (PSMA).

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.
AuthorsYogita Patil, Hilary Shmeeda, Yasmine Amitay, Patricia Ohana, Saran Kumar, Alberto Gabizon
JournalNanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 14 Issue 4 Pg. 1407-1416 (06 2018) ISSN: 1549-9642 [Electronic] United States
PMID29680672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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)

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