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

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 incr...

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Bibliographic Details
Published in:Nanomedicine 2018-06, Vol.14 (4), p.1407-1416
Main Authors: Patil, Yogita, Shmeeda, Hilary, Amitay, Yasmine, Ohana, Patricia, Kumar, Saran, Gabizon, Alberto
Format: Article
Language:English
Subjects:
Antigens, Surface - metabolism
Cell Line, Tumor
Cell Survival - drug effects
Doxorubicin
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Delivery Systems - methods
Folate receptor
Folic Acid - chemistry
Glutamate Carboxypeptidase II - metabolism
Humans
Liposomes
Liposomes - chemistry
Male
Mitomycin - chemistry
Mitomycin - pharmacology
Mitomycin-C
Prodrug
Prostate cancer
Prostatic Neoplasms - metabolism
PSMA
Targeting
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Summary: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. A folate lipophilic conjugate is grafted on pegylated liposome with co-entrapped mitomycin-c prodrug (MLP) and doxorubicin (targeted liposomes). These folate-targeted liposomes and their non-targeted controls were tested on PSMA-positive tumor cells (LNCaP) and found to deliver effectively their contents via interaction between folate ligand and PSMA. As a result, the pharmacologic activity of the drug cocktail is significantly enhanced. [Display omitted]
ISSN:1549-9634
1549-9642
DOI:10.1016/j.nano.2018.04.011