TY - JOUR
T1 - Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells
AU - Indig, Guilherme L.
AU - Anderson, Gregory S.
AU - Nichols, Michael G.
AU - Bartlett, Jeremy A.
AU - Mellon, William S.
AU - Sieber, Fritz
N1 - Funding Information:
GLI is supported in part by PharmaLux LLC. He acknowledges the University of Wisconsin‐Madison for start‐up funds and continuous financial support. MGN acknowledges the NIH (5F32 CA72225‐03) for a post doctoral fellowship, and the Developmental Resource for Biophysical Imaging and Opto‐electronics (DRBIO) at Cornell University, supported by the NIH (P412RR04224‐11) and NSF (BIR9419978/DBI9419978). FS acknowledges support from the MACC Fund and Children's Hospital Foundation.
PY - 2000/1
Y1 - 2000/1
N2 - Extensively conjugated cationic molecules with appropriate structural features naturally accumulate into the mitochondria of living cells, a phenomenon typically more prominent in tumor than in normal cells. Because a variety of tumor cells also retain pertinent cationic structures for longer periods of time compared with normal cells, mitochondrial targeting has been proposed as a selective therapeutic strategy of relevance for both chemotherapy and photochemotherapy of neoplastic diseases. Here we report that the triarylmethane dye crystal violet stains cell mitochondria with efficiency and selectivity, and is a promising candidate for photochemotherapy applications. Crystal violet exhibits pronounced phototoxicity toward L1210 leukemia cells but comparatively small toxic effects toward normal hematopoietic cells (murine granulocyte-macrophage progenitors, CFU-GM). On the basis of a comparative examination of chemical, photochemical, and phototoxic properties of crystal violet and other triarylmethane dyes, we have identified interdependencies between molecular structure, and selective phototoxicity toward tumor cells. These structure- activity relationships represent useful guidelines for the development of novel purging protocols to promote selective elimination of residual tumor cells from autologous bone marrow grafts with minimum toxicity to normal hematopoietic stem cells. (C) 2000 Wiley-Liss, Inc.
AB - Extensively conjugated cationic molecules with appropriate structural features naturally accumulate into the mitochondria of living cells, a phenomenon typically more prominent in tumor than in normal cells. Because a variety of tumor cells also retain pertinent cationic structures for longer periods of time compared with normal cells, mitochondrial targeting has been proposed as a selective therapeutic strategy of relevance for both chemotherapy and photochemotherapy of neoplastic diseases. Here we report that the triarylmethane dye crystal violet stains cell mitochondria with efficiency and selectivity, and is a promising candidate for photochemotherapy applications. Crystal violet exhibits pronounced phototoxicity toward L1210 leukemia cells but comparatively small toxic effects toward normal hematopoietic cells (murine granulocyte-macrophage progenitors, CFU-GM). On the basis of a comparative examination of chemical, photochemical, and phototoxic properties of crystal violet and other triarylmethane dyes, we have identified interdependencies between molecular structure, and selective phototoxicity toward tumor cells. These structure- activity relationships represent useful guidelines for the development of novel purging protocols to promote selective elimination of residual tumor cells from autologous bone marrow grafts with minimum toxicity to normal hematopoietic stem cells. (C) 2000 Wiley-Liss, Inc.
UR - http://www.scopus.com/inward/record.url?scp=0033965706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033965706&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1520-6017(200001)89:1<88::AID-JPS9>3.0.CO;2-K
DO - 10.1002/(SICI)1520-6017(200001)89:1<88::AID-JPS9>3.0.CO;2-K
M3 - Article
C2 - 10664541
AN - SCOPUS:0033965706
VL - 89
SP - 88
EP - 99
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 1
ER -