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

Authors :
Yasmine Amitay
Yogita Patil
Alberto Gabizon
Patricia Ohana
Hilary Shmeeda
Saran Kumar
Source :
Nanomedicine : nanotechnology, biology, and medicine. 14(4)
Publication Year :
2017

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.

Details

ISSN :
15499642
Volume :
14
Issue :
4
Database :
OpenAIRE
Journal :
Nanomedicine : nanotechnology, biology, and medicine
Accession number :
edsair.doi.dedup.....b41e3e3a66c0d08476fbf62db99a9bbf