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Nanomedicine. 2018 Jun;14(4):1407-1416. doi: 10.1016/j.nano.2018.04.011. Epub 2018 Apr 19.

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

Author information

1
Hebrew University-School of Medicine, Jerusalem, Israel.
2
Shaare Zedek Medical Center- Oncology Institute, Jerusalem, Israel.
3
Lipomedix Pharmaceuticals Ltd., Jerusalem, Israel.
4
Hebrew University-School of Medicine, Jerusalem, Israel; Shaare Zedek Medical Center- Oncology Institute, Jerusalem, Israel; Lipomedix Pharmaceuticals Ltd., Jerusalem, Israel. Electronic address: alberto.gabizon@gmail.com.

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.

KEYWORDS:

Doxorubicin; Folate receptor; Liposomes; Mitomycin-C; PSMA; Prodrug; Prostate cancer; Targeting

PMID:
29680672
DOI:
10.1016/j.nano.2018.04.011
[Indexed for MEDLINE]

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