Effect of vorinostat (V)-loaded PLGA nanoparticles (NP) surface modified with a PSMA ligand on prostate cancer (PC) cells.
2010
e13629 Background: Polymeric NP can be tuned for controlled drug delivery and SM for cell-specific targeting. To overcome V concentration and time dependent reversible growth inhibition of PC cells, we designed a NP to deliver V to PC by polymeric NP that were SM with a ligand to prostate specific membrane antigen (PSMA). Methods: V was encapsulated in poly(lactic-co-glycolic acid) (PLGA) using oil in water emulsion. Pegylated (PEG) phospholipid was added to the aqueous phase for SM, electrostatic and steric stabilization, and longer circulation in vivo. For PSMA targeting, the lipid amino end was covalently modified to possess a glutamate urea with known pM Ki binding affinity to PSMA. Four NP designs were used in cytotoxicity assays : (1) V loaded PLGA NP (V-NP), (2) V loaded PLGA NP and PSMA functionalized (V-NP-PSMA), (3) no drug and PSMA functionalized NP (Bk-NP-PSMA), (4) V loaded and unmodified PEG phospholipid (V-NP-DSPE). LNCaP and PC-3 cells (104 /well) were cultured with V (0, 0.1, 0.5, 1, 5, 1...
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