Journal article
In vitro targeted photodynamic therapy with a pyropheophorbide‐a conjugated inhibitor of prostate‐specific membrane antigen
The Prostate, Vol.69(6), pp.585-594
05/01/2009
Handle:
https://hdl.handle.net/2376/104425
PMCID: PMC2719770
PMID: 19142895
Abstract
BACKGROUND
The lack of specific delivery of photosensitizers (PSs), represents a significant limitation of photodynamic therapy (PDT) of cancer. The biomarker prostate‐specific membrane antigen (PSMA) has attracted considerable attention as a target for imaging and therapeutic applications for prostate cancer. Although recent efforts have been made to conjugate inhibitors of PSMA with imaging agents, there have been no reports on PS‐conjugated PSMA inhibitors for targeted PDT of prostate cancer. The present study focuses on the use of a PSMA inhibitor‐conjugate of pyropheophorbide‐a (Ppa‐conjugate 2) for targeted PDT to achieve apoptosis in PSMA+ LNCaP cells.
METHODS
Confocal laser scanning microscopy with a combination of nuclear staining and immunofluorescence methods were employed to monitor the specific imaging and PDT‐mediated apoptotic effects on PSMA‐positive LNCaP and PSMA‐negative (PC‐3) cells.
RESULTS
Our results demonstrated that PDT‐mediated effects by Ppa‐conjugate 2 were specific to LNCaP cells, but not PC‐3 cells. Cell permeability was detected as early as 2 hr by HOE33342/PI double staining, becoming more intense by 4 hr. Evidence for the apoptotic caspase cascade being activated was based on the appearance of poly‐ADP‐ribose polymerase (PARP) p85 fragment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay detected DNA fragmentation 16 hr post‐PDT, confirming apoptotic events.
CONCLUSIONS
Cell permeability by HOE33342/PI double staining as well as PARP p85 fragment and TUNEL assays confirm cellular apoptosis in PSMA+ cells when treated with PS‐inhibitor conjugate 2 and subsequently irradiated. It is expected that the PSMA targeting small‐molecule of this conjugate can serve as a delivery vehicle for PDT and other therapeutic applications for prostate cancer. Prostate 69:585–594, 2009. © 2009 Wiley‐Liss, Inc.
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Details
- Title
- In vitro targeted photodynamic therapy with a pyropheophorbide‐a conjugated inhibitor of prostate‐specific membrane antigen
- Creators
- Tiancheng LiuLisa Y WuJoseph K ChoiClifford E Berkman
- Publication Details
- The Prostate, Vol.69(6), pp.585-594
- Academic Unit
- Chemistry, Department of
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- Number of pages
- 10
- Grant note
- National Institutes of Health (7R21CA122126‐03)
- Identifiers
- 99900546820101842
- Language
- English
- Resource Type
- Journal article