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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / chemistry*
  • Doxorubicin / pharmacology
  • Drug Delivery Systems / methods
  • Folic Acid / chemistry*
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Liposomes / chemistry*
  • Male
  • Mitomycin / chemistry
  • Mitomycin / pharmacology
  • Prostatic Neoplasms / metabolism*


  • Antigens, Surface
  • Liposomes
  • Mitomycin
  • Doxorubicin
  • Folic Acid
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II